The Roche Cobas Vega is a five-part differential haematological analyzer evolving from the former Cobas Helios, Argos and Micros. As the leukocyte differential of Cobas Vega displays several interesting features, we analyzed its clinical performance and compared it either to three other commercial haematological analyzers (Technicon-Bayer H*2, Coulter STKS and Abbott CD-3500) or to the manual reference method, as described in the National Committee for Clinical Laboratory Standards (NCCLS) H20-A protocol. Within- and between-batch coefficients of variations (CVs) of the white blood cell differential were satisfactory and close, or even better than the ones reported for the other instruments: 0.81% (neutrophils), 1.87% (lymphocytes), 6.76% (monocytes), 7.73% (eosinophils) and 22.55% (basophils). The identification of abnormalities in the white blood cell differential was obtained either on the basis of the instrument-specific ranges or on the generation of one or more flags by comparison with results of the manual reference method. The Vega demonstrated remarkable performance in terms of specificity (90.0%), sensitivity (91.6%) and both positive (97.7%) and negative (69.1%) predictive values; likewise, the global efficiency was the best (90.3%) among the analyzers we evaluated. The flags generated in the presence of morphological abnormalities of the samples displayed excellent sensitivity (from 88.9% to 100%), specificity (from 93.5% to 98.3%) and satisfactory positive (from 51.1% to 66.7%) and negative (from 98.3% to 100%) predictive values. We conclude that the analytical performance of the new Cobas Vega haematological analyzer can significantly improve the identification of various haematological abnormalities as an important contribution to the accuracy is provided by the new staining for granulocytes.