The association between hepatitis C virus and certain B-cell non-Hodgkin lymphomas, such as marginal zone lymphomas, is supported by epidemiological studies. The exact pathogenetic mechanism is still unknown but both chronic antigenic stimulation and viral lymphotropism may contribute to the evolution of the malignant clone. Furthermore, the hematologic response following hepatitis C antiviral treatment suggests that the virus may have an etiologic role. Interferon and ribavirin based treatment proved to be successful in small case series of hepatitis C virus associated splenic lymphoma with villous lymphocytes, therefore, it is suggested that antiviral treatment could be an alternative to chemo-immunotherapy. In the near future new more potent direct acting antivirals will make interferon free treatments possible. It is still an open question whether these new short-course regimens are also effective in the treatment of associated lymphomas and what is the importance of the lymphoid reservoir in eliminating HCV.