To evaluate the impact of liver histology on the management of HCV-related chronic hepatitis, 281 patients with chronic HCV infection who consecutively underwent percutaneous liver biopsy (LB) at one of the 15 participating Italian Units of Infectious Diseases were investigated in 2005. Demographic, aetiological, laboratory and clinical data and information on methods applied to perform ultrasonography (US) and LB were recorded. Males predominated (61.6%), mean age was 47.5 years and the mean BMI 22.3. In each case LB was US-guided or US-assisted. An 18-gauge Menghini-type needle was used in 203 (72.2%) cases. The length of the specimen ranged between 1.5 and 5 cm in 279 (99.3%) cases, it was smaller in two cases, but the diagnosis was still possible. Haemoperitoneum was the only (0.4%) major unpredictable complication; minor complications were also infrequent (4%). Using both clinical and laboratory data and US examination the physician misdiagnosed liver histology in 25% of cases. After LB the physicians changed their opinion on whether to treat with PEG-INF plus ribavirin in 43 (15.5%) cases. Liver histology allows more accurate diagnosis and enables physicians to make the most appropriate choic.