diff --git a/fmriprep/workflows/base.py b/fmriprep/workflows/base.py
index 01664861..1cdac46a 100644
--- a/fmriprep/workflows/base.py
+++ b/fmriprep/workflows/base.py
@@ -580,7 +580,15 @@ def init_single_subject_wf(subject_id: str):
             suffices = [s.suffix for s in estimator.sources]
 
             if estimator.method == fm.EstimatorType.PEPOLAR:
-                if len(suffices) == 2 and all(suf in ('epi', 'bold', 'sbref') for suf in suffices):
+                # "Sophisticated" PEPOLAR schemes should be run "manually" with SDCFlows
+                # The following two cases are not considered sophisticated:
+                # 1. All PEPOLAR entities are the same modality
+                #    (typically, more than two EPI PE directions), or
+                # 2. Two modalities are involved, with at most two images to pass
+                #    into FSL TOPUP.
+                if len(set(suffices)) == 1 or (
+                    len(suffices) == 2 and all(suf in ('epi', 'bold', 'sbref') for suf in suffices)
+                ):
                     wf_inputs = getattr(fmap_wf.inputs, f'in_{estimator.bids_id}')
                     wf_inputs.in_data = [str(s.path) for s in estimator.sources]
                     wf_inputs.metadata = [s.metadata for s in estimator.sources]