To verify the clinical efficacy of the Desmet classification of chronic hepatitis C we reviewed 801 liver biopsies from patients with HCV-chronic hepatitis (CH). The diagnosis of chronic hepatitis was assessed according to the Desmet classification based on the Knodell Histological Activity Index (HAI) (minimal CH=score 1-3; mild CH= 4-8; moderate CH= 9-12; severe CH= 13-18). Liver fibrosis was assessed according to the Scheuer scoring system. One hundred forty-eight patients had cirrhosis and 653 CH. Of these 653, according to the Desmet classification 145 patients showed minimal, 424 mild, 73 moderate and 11 severe chronic hepatitis. Since the classification underestimated the moderate and severe forms of HCV-related chronic hepatitis, we evaluated the possibility of improving the Desmet classification of chronic hepatitis C using our classification: minimal CH= score 1-3; mild CH= 4-6; moderate CH= 7-8; severe CH= 9-18. According to our classification 145 showed minimal CH, 363 mild CH, 61 moderate CH and 84 severe CH. All the 61 patients who crossed over from mild CH under the Desmet to moderate CH under our classification showed a periportal inflammation of grade 3, and all the 73 patients but 8 who crossed over from moderate to severe showed a grade of periportal inflammation higher than 3. The Desmet classification of HCV-related chronic hepatitis underestimated the severe forms of HCV-CH, while our classification seems to be suitable also for chronic hepatitis C.