Four years have passed since publication of the latest update in clinical criteria for the diagnosis of polycythemia vera. During this time, the first molecular markers for polycythemia vera have been described. They include decreased expression of the thrombopoietin receptor, c-Mpl, and overexpression of the polycythemia rubra vera-1 messenger RNA. These biomarkers, which are not in themselves the causative changes leading to disease development but nonetheless appear intricately linked to the pathological process, may constitute a useful addition to our diagnostic repertoire. This review examines both the currently available clinical criteria and the possible role of biomarkers in the diagnosis of polycythemia vera. From this discussion, a refined set of diagnostic criteria for polycythemia vera is proposed.