The treatment of patients with non-Hodgkin's lymphoma (NHL) may be complicated by concomitant chronic hepatitis C virus (HCV) infection. Recent data suggest that HCV may also be a contributing factor to the development of this disease. Although antiviral treatment has occasionally been reported to result in the regression of lymphoma in patients with HCV infection, the importance of the control of this infection on the prognosis of lymphoma needs to be defined. Here we report a patient with diffuse large B-cell lymphoma who presented with a mass in her left breast. She had had HCV-related liver cirrhosis for 6 years. She was given rituximab monotherapy for three consecutive weeks, but treatment had to be discontinued as a result of hematological toxicity. HCV viral load also increased, but then decreased gradually after rituximab was stopped. She could be given no further therapy. Six months later she presented with spinal involvement with infiltration of the cauda equina. Though cranial-spinal radiotherapy and steroids were started, she died shortly thereafter. Though rituximab is an invaluable drug in the treatment of B-cell lymphomas, we believe that the use of such agents with potentially long-lasting effects on B lymphocytes requires extended vigilance for accelerated replication of hepatitis B and C viruses.