We evaluated the performance of the CAPILLARYS 2 (Sebia, Norcross, GA) capillary electrophoresis system for detection and identification of monoclonal proteins in serum samples. We analyzed 104 serum specimens by Sebia Hydragel serum protein electrophoresis (agarose gel electrophoresis [AGE]/immunofixation electrophoresis [IFE]) and CAPILLARYS 2 capillary zone electrophoresis (CZE)/immunosubtraction. AGE and CZE had sensitivities of 90% and 81%, respectively, based on IFE as the "gold standard," and all bands detected were confirmed by IFE (100% specificity). AGE and CZE had an overall agreement of 91% on serum protein electrophoresis. In the population tested, IgG was detected in 29% of samples by IFE and 30% using immunosubtraction. Similarly IgA was detected in 9% of cases by IFE and 8% by immunosubtraction. IgM and light chains were detected in 6% and 3% of cases, respectively, by IFE, whereas CZE/immunosubtraction did not detect any IgM or light chains. In our hands, AGE and CZE had the same specificity for detection of monoclonal proteins; however, CZE/immunosubtraction seems to be less sensitive than IFE for the detection of IgM and, possibly, serum light chains. © American Society for Clinical Pathology.