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Cryoglobulinemia may be a symptomless phenomenon that is incidentally found, or it may produce a clinical syndrome involving the skin as a primary organ. In a historic large-scale examination, 11% of patient sera were shown to have cyoglobulinemia, but detection rates vary greatly with the patient population studied.1 Reliable figures on the incidence or prevalence of cryoglobulinemia or symptomatic cryoglobulinemic syndrome are lacking. The epidemiologic study is hampered by factors such as selection bias from the referral of patients to tertiary care hospitals, by the heterogeneity of clinical presentations inclusion criteria, and by the different geographic distribution of underlying etiologies such as HCV infection. There is a geographic predominance of cryoglobulinemia in Southern Europe as compared to Northern Europe or the United States that might be explained by this latter fact. The frequency distribution of different cryoglobulinemia subtypes among all types of cryoglobulinemia is approximately type I 25%, type II 25%, type III 50%, making the mixed cryoglobulinemias (types II and III) the most abundant form.2 The vast majority (>90%) of mixed cryoglobulinemias occurs in association with chronic HCV infection. Thus, HCV-associated mixed cryoglobulinemia is the form among all cryoglobulinemias that has been studied best. On average, 30% of chronically HCV-infected subjects develop cryoglobulinemia, and this proportion can go up to 90% when patients with very longstanding disease are examined.3–5 Development of cryoglobulins is more frequent with HCV genotype 1 as compared to genotypes 2 and 3.6 However, on average, the symptomatic cryoglobulinemic vasculitis syndrome is present in only 2% to 5% of chronically HCV-infected patients7 though figures as high ...