Prospective studies of patients with cirrhosis who are at risk for developing hepatocellular carcinoma (HCC), have greatly improved our understanding of the natural history of this tumour. Despite many studies, the controversy of whether HCC originates from one or more than one clone of transformed liver cells is still unsettled. The natural history of HCC in many instances is an extension of that of the underlying cirrhosis, although the course of the tumour disease may vary from patient to patient and in different geographical areas. In Oriental and southern European patients with HCC, a longer time may elapse between diagnosis and death, than in African blacks. The information about tumour development in non-cirrhotic liver is scanty, due to the little known risk factors for this type of tumour which has impeded performing prospective cohort studies of high risk patients.