Chronic HCV infection has been implicated in the induction and maintenance of B-cell lymphomas. The strongest evidence for this comes from clinical observations of tumor regressions upon anti-viral treatments. Here we used multiple methods to test the hypothesis that the expansion of HCV-specific B cells gives rise to lymphomas. We obtained lymphoma tissues from HCV-infected lymphoma patients, including some that later regressed upon anti-viral treatments. We expressed the lymphoma B-cell receptors (BCRs) as soluble IgGs and membrane IgMs, and analyzed their reactivity with HCV proteins and with HCV virions. We confirmed previous reports that HCV-associated lymphomas use a restricted immunoglobulin variable region (V) gene repertoire. However, we found no evidence for their binding to the HCV antigens. We conclude that most lymphomas of HCV-infected patients do not arise from B cells aimed at eliminating the virus.