Hepatocellular carcinoma (HCC) is the most common histological form of primary liver cancer; the tumor cells having retained features of hepatocytic differentiation. It is important to emphasize the heterogeneity of the histological background on which the tumor develops. Most HCCs complicate the evolution of an active or inactive cirrhosis. However, some tumors occur on livers with minimal histological changes; the prevalence of such cases varies from one geographical region to the other; being much higher in the southern half of Africa (around 40% of HCCs) than in Asia, America and Europe, where at least 90% of HCCs are associated in the cirrhosis. This heterogeneity is probably a reflection of different environmental and genetic factors. A large number of epidemiological and molecular studies have indeed clearly demonstrated the prime importance of environmental factors to the development of primary liver cancers in humans. Chronic hepatitis B (HBV) and C (HCV) infections are major risk factors. This review will mainly analyse the impact of chronic HBV infection but it is important to emphasize the potential synergistic effects between HBV and HCV, as well as between viral infections and other environmental factors, such as alcohol, chemical carcinogens (see review by Dr Wogan) and other, still poorly defined, hormonal factors which may account for the higher incidence of the tumor in man. Finally the review by Dr Buendia highlights the emerging issue of liver-cancer genetics.