diff --git a/actions/ost-compare-structures b/actions/ost-compare-structures
index f2b9a58565f630d6a7757d4e4e0f7915aca723a5..cc145d048a211fe23832fab55349bb82a0cd687e 100644
--- a/actions/ost-compare-structures
+++ b/actions/ost-compare-structures
@@ -654,6 +654,11 @@ def _Main():
 
     args = _ParseArgs()
     try:
+        compute_cad = args.cad_score or args.local_cad_score
+        if compute_cad and not args.residue_number_alignment:
+            raise RuntimeError("Only support CAD score when residue numbers in "
+                               "model and reference match. Use -rna flag if "
+                               "this is the case.")
         reference = _LoadStructure(args.reference,
                                    sformat=args.reference_format,
                                    bu_idx=args.reference_biounit,