Family history and hepatitis B virus (HBV) infection have been identified as risk factors for hepatocellular carcinoma. We report hepatocellular carcinoma (HCC) diagnosed at the same time in identical twin brothers. Serological analyses of the patients showed that both were chronically infected with HBV. Molecular analyses of the tumor specimens confirmed loss of heterozygocity of the Rb gene region. Both of the patients were unresponsive to chemotherapy and died within the same month with an interval of 1 wk. With a review of the current literature, we discuss the role of HBV infection and genetic factors on hepatic carcinogenesis.