Multiple myeloma is a haematological cancer caused by malignant plasma cells in the bone marrow that can result in organ dysfunction and death. Recent novel treatments have contributed to improved survival rates, including monoclonal antibody therapies that target the CD38 protein on the surface of plasma cells. Anti-CD38 therapies are IgG kappa monoclonal antibodies that are given in doses high enough for the drug to be visible on serum protein electrophoresis as a small paraprotein. We present a case where isatuximab, the most recent anti-CD38 monoclonal antibody to be approved for treatment of myeloma, obscured the patient’s paraprotein on gel immunofixation, so that complete remission could not be demonstrated. This was resolved using the isatuximab Hydrashift assay. The interference on gel immunofixation was unexpected because isatuximab migrated in a position distinct from the patient’s paraprotein on capillary zone electrophoresis. We demonstrate the surprising finding that isatuximab migrates in a different position on gel electrophoresis compared to capillary zone electrophoresis. It is vital that laboratories are aware of the possible interference on electrophoresis from anti-CD38 monoclonal antibody therapies, and are able to recognise these drugs on protein electrophoresis. The difference in isatuximab’s electrophoretic mobility on capillary and gel protein electrophoresis makes this particularly challenging. Laboratories should have a strategy for alternative analyses in the event that the drugs interfere with assessment of the patient’s paraprotein.