- An association between chronic hepatitis C (HCV) infection and non-Hodgkin's lymphoma has been reported. We carried out this study to evaluate the possibility of an association between HCV infection and other extrahepatic malignancies. The medical records of 103 unselected, consecutively chosen, anti HCV-positive and 105 hepatitis B surface antigen (HBsAg)-positive patients attending the liver clinic or hospitalized in the Department of Medicine were reviewed. Patients in whom anti-HCV positivity was detected after the malignancy was diagnosed were excluded. Malignancy rates in the general Israeli population were obtained from the Israeli cancer registry. The ages of anti-HCV-positive and HBsAg-positive patients were 54 +/- 16 (+/-SD) (range, 15-84) and 45 +/- 12 (range, 20-78) years, respectively; the male/female ratios were 50/53 and 73/32, respectively. Extrahepatic malignancies were found in 15 (14.6%) of the anti-HCV and in three (2.9%) of the HBsAg-positive patients. Thirteen of the malignancies were found among the 60 anti-HCV-positive patients aged > or =55 years old. Only one malignancy was found among the 28 HBsAg-positive patients of the same age group (p < 0.01). The rate of extrahepatic malignancies in these HCV-infected patients was significantly higher (p < 0.01) than expected in the general population. An association between HCV infection and extrahepatic malignancy may exist, but further prospective studies, including a large number of patients with HCV infection, will be necessary to define this observation.