We performed a retrospective study to determine the prevalence of hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis G virus (HGV) genomes in formalin-fixed, paraffin-embedded liver tissues from hepatocellular carcinoma (HCC) patients in various geographic areas. The prevalence of each hepatitis virus in the liver tissues that have both carcinoma and noncarcinoma regions was different among the countries. HCV was the most prevalent in Japan (75 of 122 [61.5%]), Spain (9 of 15 [60%]), and the United States (27 of 65 [41.5%]); HBV was the most prevalent in Korea (45 of 55 [82%]) and among Japanese Americans in Hawaii (4 of 8 [50%]). Genotype II/1b was the most common genotype of HCV encountered in HCCs in these countries. In contrast, HGV RNA was undetectable in all tested HCCs. "Cryptogenic HCC," defined as HCC of unknown etiology, was seen 4 (3%) and 4 (6.2%) of Japanese and American patients, respectively, but this was not found in other countries. Interestingly, patients with HCC related to primary biliary cirrhosis (4.6%), who were excluded from analysis as hepatitis virus infections, were present only in the United States, but not in other countries. This study suggests that HCV, particularly genotype II/1b, and HBV may play an important role in hepatocarcinogenesis in these countries. There was no evidence of any relation between HGV infection and development of HCC.