Summary Background: Capillary electrophoresis (CE) is used for the screening of protein abnormalities in serum and other biological fluids. Since the Helena V8 CE system has been recently commercialized, the aim of this study was to assess its analytical performance under routine laboratory conditions. Methods: The evaluation of Helena V8 (Medical Systems S.p.A., Genova, Italy) for protein fractions (i.e., albumin, alpha-1, alpha-2, beta-1, beta-2, gamma, albumin/globulin ratio [A/G]) and monoclonal component (MC) quantification included imprecision studies, linearity, and comparison with Sebia Capillarys (Sebia, Evry Cedex, France), which was considered the reference analyzer. Results: The imprecision of Helena V8 on all parameters was comprised between 0.8% and 15.2%; the linearity was excellent up to an MC value of 14.5% (r=1.00). The comparison studies showed excellent Spearman’s correlations with Sebia Capillarys, with coefficients comprised between 0.84 and 0.99 (all p<0.001). The mean bias of Helena V8 versus Sebia Capillarys was -0.02% for G/A, -0.2% for albumin, 2.1% for alpha-1, 0.1% for alpha-2, 0.3% for beta-1, -0.2% for beta-2, -2.2% for gamma and 1 g/L for MC. Conclusions: The results of this evaluation attest that Helena V8 is a suitable alternative for routine separation and quantification of protein fractions and monoclonal component.