Primary biliary cirrhosis is considered a low risk for the development of hepatocellular carcinoma. We evaluated the incidence of hepatocellular carcinoma in a cohort of 89 female primary biliary cirrhosis patients and, as a control group in 73 female patients with cirrhosis of a different etiology. The patients underwent ultrasound and alfa-fetoprotein determination every 6 months. Two patients developed hepatocellular carcinoma in the primary biliary cirrhosis and three in the control group, respectively. The Relative Risk for hepatocellular carcinoma in primary biliary cirrhosis patients was 0.7. However, when considering only stage IV, primary biliary cirrhosis patients with cirrhosis, the Relative Risk was actually 1.5 with respect to controls, with 1.4% cases of hepatocellular carcinoma per year. These data suggest that the risk of hepatocellular carcinoma is similar in female patients with primary biliary cirrhosis and in female patients with cirrhosis of a different etiology.