One patient with the fibrolamellar variant of hepatocellular carcinoma was found to be seropositive for HBsAg and anti-HBe. DNA from tumor and nontumor areas of the liver was examined by molecular hybridization for hepatitis B virus DNA sequences. Undigested DNA from the tumor gave a high-molecular-weight smear, and restriction-enzyme analysis indicated a single instance of integration. Nontumor liver tissue was analyzed from three separate areas. Hepatitis B virus DNA was detected in two of these; restriction-enzyme digestion suggested they contained different sites of viral integration. As with the typical hepatitis B virus-related hepatocellular carcinoma, analysis of hepatitis B virus DNA from nontumorous liver yielded a different pattern of high-molecular-weight bands, indicating that the virus genome had integrated at different chromosomal locations than that seen in the tumor. The finding of integrated hepatitis B virus DNA, especially in tumorous but also in nontumorous liver, would be consistent with an oncogenic role for hepatitis B virus in certain instances of fibrolamellar tumors and in the more typical hepatitis B virus-related hepatocellular carcinoma.