The incidence of hepatocellular carcinoma (HCC) in Japan has increased over the past two decades. Of the 379 patients with HCC treated at Shinshu University Hospital over the past 20 years, 112 underwent treatment between 1971 and 1980 and 267 were treated between 1981 and 1990. The prevalence of hepatitis B virus-associated HCC and hepatitis C virus-associated HCC was 54% and 34%, respectively, during the first decade and 31% and 60%, respectively, during the second decade. Major factors contributing to the increased incidence of HCC include an increase in the incidence of type C chronic hepatitis and an increase in the incidence of cirrhosis of the liver, which in turn are the result of blood transfusions received about 30 years ago. Donated blood testing positive for hepatitis C virus antibody is currently rejected from the blood supply. However, the occurrence of post-transfusion hepatitis with the potential to develop into HCC has not been entirely eliminated. In addition, there is an as yet unelucidated route of horizontal transmission of hepatitis C virus.