A 59-year-old lady presented with recurrent angioedema without urticaria. The clinical history and examination were consistent with an acquired C1 esterase deficiency secondary to lymphoproliferative disease. Despite a low C1 esterase level, the C4 level assayed by nephelometry on our automated analyser was normal. Analysis using different nephelometric analysers revealed consistently low C4, despite consistent normal readings in our analyser. Further investigation revealed an IgM-kappa paraprotein that seemed to interfere with both this and haematology coagulation assays. Splenic marginal zone lymphoma was confirmed on bone marrow biopsy. Monoclonal paraproteins may interfere with nephelometric, turbidimetric and immunological assays in a non-antibody-specific manner and should be considered when there are unusual or unexpected results, particularly in a patient with lymphoproliferative disease.