Chronic infection with hepatitis B virus (HBV) has been reported in two-thirds of cases of hepatocellular carcinoma (HCC) in Greece from 1973 to 1995, while chronic hepatitis C virus (HCV) infection in 10% of them. We studied the roles of HBV and HCV in HCC in Greece between 1996 and 2000 compared with the past, and possible differences in clinical and laboratory characteristics of HBV- and HCV-related HCC. Complete clinical and laboratory data from 306 patients with HCC, diagnosed from January 1996 to December 2000, were analyzed. Chronic HBV and HCV infection were detected in 52.3 and 21.6% of the patients, respectively. The ratio of HBV- to HCV-related HCC was 2.42. Compared with the data prior to 1996, there was a 101.8% increase in the relative frequency of HCV (P < 0.0001) and an 11.8% decrease in that of HBV (P = 0.033), with a -56.3% change in the ratio of HBV- to HCV-related HCC cases. Statistically significant differences in the male/female ratio, median age and frequency of multifocal lesions were found in HBV- vs HCV-related HCC. Although HBV still represents the major aetiological factor of HCC in Greece, its role has significantly decreased in the last 5 years, while a more significant increase has occurred in HCV-related HCC. The two aetiological types of HCC differ in Greece in demographic, epidemiological and other features.