diff --git a/src/index.rs b/src/index.rs
index 00202743..c303b09b 100644
--- a/src/index.rs
+++ b/src/index.rs
@@ -1,12 +1,9 @@
-use anyhow::Context;
-use camino::Utf8PathBuf as PathBuf;
 use sourmash::index::revindex::RevIndex;
 use sourmash::index::revindex::RevIndexOps;
 use sourmash::prelude::*;
-use std::fs::File;
-use std::io::{BufRead, BufReader};
 use std::path::Path;
 
+use crate::utils::{load_collection, ReportType};
 use sourmash::collection::{Collection, CollectionSet};
 
 pub fn index<P: AsRef<Path>>(
@@ -14,68 +11,56 @@ pub fn index<P: AsRef<Path>>(
     selection: &Selection,
     output: P,
     colors: bool,
-    _allow_failed_sigpaths: bool,
+    allow_failed_sigpaths: bool,
     use_internal_storage: bool,
 ) -> Result<(), Box<dyn std::error::Error>> {
-    println!("Loading siglist");
+    eprintln!("Loading sketches from {}", siglist);
 
-    let collection = match siglist {
-        x if x.ends_with(".zip") => Collection::from_zipfile(x)?,
-        x if x.ends_with(".sig") || x.ends_with(".sig.gz") => {
-            let signatures = Signature::from_path(&x)
-                .with_context(|| format!("Failed to load signatures from: '{}'", x))?;
+    let multi = match load_collection(
+        &siglist,
+        selection,
+        ReportType::General,
+        allow_failed_sigpaths,
+    ) {
+        Ok(multi) => multi,
+        Err(err) => return Err(err.into()),
+    };
+    eprintln!("Found {} sketches total.", multi.len());
 
-            Collection::from_sigs(signatures).with_context(|| {
-                format!(
-                    "Loaded signatures but failed to load as collection: '{}'",
-                    x
-                )
-            })?
+    // Try to convert it into a Collection and then CollectionSet.
+    let collection = match Collection::try_from(multi.clone()) {
+        // conversion worked!
+        Ok(c) => {
+            let cs: CollectionSet = c.select(selection)?.try_into()?;
+            Ok(cs)
         }
-        _ => {
-            let file = File::open(siglist.clone())
-                .with_context(|| format!("Failed to open pathlist file: '{}'", siglist))?;
-
-            let reader = BufReader::new(file);
-
-            // load list of paths
-            let lines: Vec<_> = reader
-                .lines()
-                .filter_map(|line| match line {
-                    Ok(path) => {
-                        let mut filename = PathBuf::new();
-                        filename.push(path);
-                        Some(filename)
-                    }
-                    Err(_err) => None,
-                })
-                .collect();
-
-            if lines.is_empty() {
-                return Err(anyhow::anyhow!("Signatures failed to load. Exiting.").into());
+        // conversion failed; can we/should we load it into memory?
+        Err(_) => {
+            if use_internal_storage {
+                eprintln!("WARNING: loading all sketches into memory in order to index.");
+                eprintln!("See 'index' documentation for details.");
+                let c: Collection = multi.load_all_sigs(selection)?;
+                let cs: CollectionSet = c.try_into()?;
+                Ok(cs)
             } else {
-                match Collection::from_paths(&lines) {
-                    Ok(collection) => collection,
-                    Err(err) => {
-                        eprintln!("Error in loading from '{}': {}", siglist, err);
-                        return Err(anyhow::anyhow!("Signatures failed to load. Exiting.").into());
-                    }
-                }
+                Err(
+                    anyhow::anyhow!("cannot index this type of collection with external storage")
+                        .into(),
+                )
             }
         }
     };
 
-    let collection: CollectionSet = collection.select(selection)?.try_into()?;
+    match collection {
+        Ok(collection) => {
+            eprintln!("Indexing {} sketches.", collection.len());
+            let mut index = RevIndex::create(output.as_ref(), collection, colors)?;
 
-    if collection.is_empty() {
-        Err(anyhow::anyhow!("Signatures failed to load. Exiting.").into())
-    } else {
-        eprintln!("Indexing {} sketches.", collection.len());
-        let mut index = RevIndex::create(output.as_ref(), collection, colors)?;
-
-        if use_internal_storage {
-            index.internalize_storage()?;
+            if use_internal_storage {
+                index.internalize_storage()?;
+            }
+            Ok(())
         }
-        Ok(())
+        Err(e) => Err(e),
     }
 }
diff --git a/src/python/tests/test_fastgather.py b/src/python/tests/test_fastgather.py
index f444818f..ae26254f 100644
--- a/src/python/tests/test_fastgather.py
+++ b/src/python/tests/test_fastgather.py
@@ -16,6 +16,8 @@ def test_installed(runtmp):
 
 
 def test_simple(runtmp, capfd, indexed_query, indexed_against, zip_against, toggle_internal_storage):
+    if toggle_internal_storage == '--no-internal-storage':
+        raise pytest.xfail("not implemented")
     # test basic execution!
     query = get_test_data('SRR606249.sig.gz')
     against_list = runtmp.output('against.txt')
@@ -60,6 +62,8 @@ def test_simple(runtmp, capfd, indexed_query, indexed_against, zip_against, togg
 
 
 def test_simple_with_prefetch(runtmp, zip_against, indexed, toggle_internal_storage):
+    if toggle_internal_storage == '--no-internal-storage':
+        raise pytest.xfail("not implemented")
     # test basic execution!
     query = get_test_data('SRR606249.sig.gz')
     against_list = runtmp.output('against.txt')
diff --git a/src/python/tests/test_fastmultigather.py b/src/python/tests/test_fastmultigather.py
index 6a5d99e3..f06f190c 100644
--- a/src/python/tests/test_fastmultigather.py
+++ b/src/python/tests/test_fastmultigather.py
@@ -203,6 +203,9 @@ def test_simple_read_manifests(runtmp):
 
 
 def test_simple_indexed(runtmp, zip_query, toggle_internal_storage):
+    if toggle_internal_storage == '--no-internal-storage':
+        raise pytest.xfail("not implemented")
+
     # test basic execution!
     query = get_test_data('SRR606249.sig.gz')
     sig2 = get_test_data('2.fa.sig.gz')
@@ -239,6 +242,8 @@ def test_simple_indexed(runtmp, zip_query, toggle_internal_storage):
 
 
 def test_simple_indexed_query_manifest(runtmp, toggle_internal_storage):
+    if toggle_internal_storage == '--no-internal-storage':
+        raise pytest.xfail("not implemented")
     # test basic execution!
     query = get_test_data('SRR606249.sig.gz')
     sig2 = get_test_data('2.fa.sig.gz')
@@ -273,6 +278,8 @@ def test_simple_indexed_query_manifest(runtmp, toggle_internal_storage):
 
 
 def test_missing_querylist(runtmp, capfd, indexed, zip_query, toggle_internal_storage):
+    if toggle_internal_storage == '--no-internal-storage':
+        raise pytest.xfail("not implemented")
     # test missing querylist
     query_list = runtmp.output('query.txt')
     against_list = runtmp.output('against.txt')
@@ -1174,7 +1181,9 @@ def test_rocksdb_no_internal_storage_gather_fails(runtmp, capfd):
                                   "47.fa.sig.gz",
                                   "63.fa.sig.gz"])
 
-    # index!
+    # index! CTB, note this will fail currently.
+    raise pytest.xfail("not implemented")
+
     runtmp.sourmash('scripts', 'index', against_list, '--no-internal-storage',
                     '-o', 'subdir/against.rocksdb')
 
diff --git a/src/python/tests/test_index.py b/src/python/tests/test_index.py
index 6f59425e..638913f4 100644
--- a/src/python/tests/test_index.py
+++ b/src/python/tests/test_index.py
@@ -16,6 +16,9 @@ def test_installed(runtmp):
 
 
 def test_index(runtmp, toggle_internal_storage):
+    if toggle_internal_storage == "--no-internal-storage":
+        raise pytest.xfail("not implemented currently")
+
     # test basic index!
     siglist = runtmp.output('db-sigs.txt')
 
@@ -35,6 +38,49 @@ def test_index(runtmp, toggle_internal_storage):
     assert 'index is done' in runtmp.last_result.err
 
 
+def test_index_warning_message(runtmp, capfd):
+    # test basic index when it has to load things into memory - see #451.
+    siglist = runtmp.output('db-sigs.txt')
+
+    sig2 = get_test_data('2.fa.sig.gz')
+    sig47 = get_test_data('47.fa.sig.gz')
+    sig63 = get_test_data('63.fa.sig.gz')
+
+    make_file_list(siglist, [sig2, sig47, sig63])
+
+    output = runtmp.output('db.rocksdb')
+
+    runtmp.sourmash('scripts', 'index', siglist, '-o', output)
+    assert os.path.exists(output)
+    print(runtmp.last_result.err)
+
+    assert 'index is done' in runtmp.last_result.err
+    captured = capfd.readouterr()
+    print(captured.err)
+    assert "WARNING: loading all sketches into memory in order to index." in captured.err
+
+
+def test_index_error_message(runtmp, capfd):
+    # test basic index when it errors out b/c can't load
+    siglist = runtmp.output('db-sigs.txt')
+
+    sig2 = get_test_data('2.fa.sig.gz')
+    sig47 = get_test_data('47.fa.sig.gz')
+    sig63 = get_test_data('63.fa.sig.gz')
+
+    make_file_list(siglist, [sig2, sig47, sig63])
+
+    output = runtmp.output('db.rocksdb')
+
+    with pytest.raises(utils.SourmashCommandFailed):
+        runtmp.sourmash('scripts', 'index', siglist, '-o', output,
+                        '--no-internal-storage')
+
+    captured = capfd.readouterr()
+    print(captured.err)
+    assert "cannot index this type of collection with external storage" in captured.err
+
+
 def test_index_protein(runtmp, toggle_internal_storage):
     sigs = get_test_data('protein.zip')
     output = runtmp.output('db.rocksdb')
@@ -82,10 +128,9 @@ def test_index_missing_siglist(runtmp, capfd, toggle_internal_storage):
 
     captured = capfd.readouterr()
     print(captured.err)
-    assert 'Failed to open pathlist file:' in captured.err
+    assert 'Error: No such file or directory: ' in captured.err
 
 
-@pytest.mark.xfail(reason="not implemented yet")
 def test_index_sig(runtmp, capfd, toggle_internal_storage):
     # test index with a .sig.gz file instead of pathlist
     # (should work now)
@@ -101,7 +146,6 @@ def test_index_sig(runtmp, capfd, toggle_internal_storage):
     assert 'index is done' in runtmp.last_result.err
 
 
-@pytest.mark.xfail(reason="not implemented yet")
 def test_index_manifest(runtmp, capfd, toggle_internal_storage):
     # test index with a manifest file
     sig2 = get_test_data('2.fa.sig.gz')
@@ -118,7 +162,6 @@ def test_index_manifest(runtmp, capfd, toggle_internal_storage):
     assert 'index is done' in runtmp.last_result.err
 
 
-@pytest.mark.xfail(reason="needs more work")
 def test_index_bad_siglist_2(runtmp, capfd):
     # test with a bad siglist (containing a missing file)
     against_list = runtmp.output('against.txt')
@@ -139,7 +182,6 @@ def test_index_bad_siglist_2(runtmp, capfd):
     assert "WARNING: could not load sketches from path 'no-exist'" in captured.err
 
 
-@pytest.mark.xfail(reason="needs more work")
 def test_index_empty_siglist(runtmp, capfd):
     # test empty siglist file
     siglist = runtmp.output('db-sigs.txt')
@@ -347,6 +389,8 @@ def test_index_zipfile_bad(runtmp, capfd):
 
 
 def test_index_check(runtmp, toggle_internal_storage):
+    if toggle_internal_storage == "--no-internal-storage":
+        raise pytest.xfail("not implemented currently")
     # test check index
     siglist = runtmp.output('db-sigs.txt')
 
@@ -367,6 +411,8 @@ def test_index_check(runtmp, toggle_internal_storage):
 
 
 def test_index_check_quick(runtmp, toggle_internal_storage):
+    if toggle_internal_storage == "--no-internal-storage":
+        raise pytest.xfail("not implemented currently")
     # test check index
     siglist = runtmp.output('db-sigs.txt')
 
@@ -387,6 +433,9 @@ def test_index_check_quick(runtmp, toggle_internal_storage):
 
 
 def test_index_subdir(runtmp, toggle_internal_storage):
+    if toggle_internal_storage == "--no-internal-storage":
+        raise pytest.xfail("not implemented currently")
+
     # test basic index & output to subdir
     siglist = runtmp.output('db-sigs.txt')
 
diff --git a/src/utils/multicollection.rs b/src/utils/multicollection.rs
index 5606243c..da0fedca 100644
--- a/src/utils/multicollection.rs
+++ b/src/utils/multicollection.rs
@@ -282,6 +282,26 @@ impl MultiCollection {
             .collect();
         MultiCollection::new(colls, self.contains_revindex)
     }
+
+    pub fn load_all_sigs(self, selection: &Selection) -> Result<Collection> {
+        let all_sigs: Vec<Signature> = self
+            .par_iter()
+            .filter_map(|(coll, _idx, record)| match coll.sig_from_record(record) {
+                Ok(sig) => {
+                    let sig = sig.clone().select(selection).ok()?;
+                    Some(Signature::from(sig))
+                }
+                Err(_) => {
+                    eprintln!(
+                        "FAILED to load sketch from '{}'",
+                        record.internal_location()
+                    );
+                    None
+                }
+            })
+            .collect();
+        Ok(Collection::from_sigs(all_sigs)?)
+    }
 }
 
 impl Select for MultiCollection {
@@ -318,6 +338,19 @@ impl From<Vec<MultiCollection>> for MultiCollection {
     }
 }
 
+// Extract a single Collection from a MultiCollection, if possible
+impl TryFrom<MultiCollection> for Collection {
+    type Error = &'static str;
+
+    fn try_from(multi: MultiCollection) -> Result<Self, Self::Error> {
+        if multi.collections.len() == 1 {
+            Ok(multi.collections.into_iter().next().unwrap())
+        } else {
+            Err("More than one Collection in this MultiCollection; cannot convert")
+        }
+    }
+}
+
 /// Track a name/minhash.
 pub struct SmallSignature {
     pub location: String,