Abstract Background: Protein and immunofixation electrophoresis of serum and urine are established as diagnostic aids for identifying monoclonal gammopathies. However, many patient sera sent to laboratories are not accompanied by urine samples and recent reports suggest the use of serum free light chain (sFLC) analysis in combination with serum protein electrophoresis (SPE) and immunofixation electrophoresis (IFE) could eliminate the need for urinalysis. The aim of the study was to assess the utility of sFLC measurement in addition to serum protein electrophoresis in the identification of patients with B-cell malignancies. Methods: A total of 952 serum samples were analysed by serum protein electrophoresis and those with abnormal bands were analysed by immunofixation. sFLCs were measured in a retrospective manner by automated assay. Results: In our study of 952 patient sera, it was found that FLC analysis identified 23 additional cases of B-cell malignancies which were missed by SPE. Conclusions: The additional malignancies identified by sFLC analysis add support for its inclusion in the routine screening protocol for B-cell malignancies. Clin Chem Lab Med 2009;47.