AIMS: Hepatocellular carcinoma (HCC) frequently develops in patients with chronic viral hepatitis, especially in the cirrhotic stage. We retrospectively studied whether the presence of the putative preneoplastic lesions large liver cell dysplasia (LLCD) and/or small liver cell dysplasia (SLCD) in a needle liver biopsy of these patients are a risk factor for the development of HCC. Methods and results: The presence of LLCD and SLCD in the needle liver biopsy taken at the initial work-up of 115 patients with chronic hepatitis B or C was assessed retrospectively. LLCD and SLCD were present in the initial biopsy of, respectively, 35 (30%) and 25 patients (22%). During a mean follow-up of 107 months, 16 patients (14%) developed HCC and this occurred significantly more frequently in patients with cirrhosis, age > or = 55 years, LLCD or SLCD. Cirrhosis and LLCD were independent risk factors for HCC development. CONCLUSIONS: Our findings indicate that the presence of LLCD in a needle liver biopsy of patients with viral-induced chronic liver disease is an independent risk factor for the development of HCC. If these results are confirmed, the presence of LLCD can be used to identify a subgroup of patients at high risk for HCC requiring more intensive screening.