A cohort of 148 consecutive patients with hepatitis C virus infection were studied at the rheumatology out-patient clinic of a tertiary care teaching hospital. The diagnosis of hepatitis C virus infection was supported by detection of HCV RNA in the serum. Cryoglobulin screening was done in all patients and the presence of a monoclonal component was investigated when the cryocrit was higher than 1%. Patients with lymphoproliferative disorders were further investigated. Four patients had a B lymphoproliferative disorder, which represents a prevalence of 2.7% in this cohort of patients with hepatitis C virus infection. Mixed cryoglobulinemia (MC), with cryocrit higher than 1%, was found in 16 of 148 patients (11%). It was type III MC in 13 patients and type II MC in 3. All patients who developed a B lymphoproliferative disorder had mixed cryoglobulinemia, with a monoclonal component (type II MC) in two patients and without a monoclonal component (type III MC) in the other two. The incidence of B-lymphoproliferative disorders among this cohort of patients with hepatitis C virus infection seems to be significantly increased. However, the high frequency of asymptomatic, undiagnosed HCV infection among the apparently healthy general population may decrease the true significance of this association. Systematic screening of cryoglobulin production in patients with hepatitis C virus infection might clarify whether the risk of B lymphoproliferative disorders increases when type II or type III mixed cryoglobulinemia is present.