This article documents five families with clusters of hepatocellular carcinoma (HCC), including one in which three successive generations were involved. All the 12 patients in these five families and 96.3% of the patients in 54 families with solitary cases of HCC seen during the same period were hepatitis B surface antigen (HBsAg)-positive. The prevalence of HBsAg in families with clusters and solitary cases of HCC was compared. The clustering of HCC in the five families reported could not be accounted for by a higher HBsAg carrier rate or an earlier age of onset of the hepatitis B virus infection. An attempt was made to identify the factors that determine the development of HCC in HBsAg carriers.