The overexpression of p53 protein and the Ki67 proliferative index was evaluated in 96 hepatocellular carcinomas (HCC), 67 in cirrhotic livers and 29 in non-cirrhotic ones, and in 13 non-carcinomatous lesions, all surgically resected from Italian patients. Overexpression of p53 was detected only in carcinomatous lesions, and was significantly related to the grade of HCC (P < 0.001). In fact, p53 was observed in 7/7 (100%) cases of grade IV, 13/43 (30.3%) of grade III, and 10/46 (21.7%) of grade II. The relationship between p53 and Ki67 scores was determined in serial sections from corresponding areas of both diffuse and patchy immunoreactivity. In the overall population, p53-positive tumors showed a significantly higher Ki67 score (15.9 +/- 5.5% vs 9.2 +/- 4.3% [P < 0.001]). This observation was evident in all grades of HCC.