The relationship between selected aspects of medical history and the risk of primary liver cancer was analyzed in a hospital-based case-control study conducted in Northern Italy on 242 patients with histologically or serologically confirmed hepatocellular carcinoma and 1169 controls in hospital for acute, nonneoplastic, or digestive diseases. Significant associations were observed for clinical history of hepatitis [odds ratio (OR), 3.7; 95% confidence interval (CI), 2.3-5.9], cirrhosis (OR, 16.8; 95% CI, 9.8-28.8), and three or more episodes of transfusion in the past (OR, 2.2; 95% CI, 1.4-4.1). Among other diseases considered, there was a significant association with diabetes (OR, 2.5; 95% CI, 1.7-3.8), and a protection by history of drug allergies (OR, 0.5; 95% CI, 0.2-0.9). These associations were not appreciably modified by allowance for major identified potential confounding factors and were observed for diseases occurring less than 5 or 5 or more years before liver cancer diagnosis, although for cirrhosis the risk was higher in the short term occurrences (OR, 50). For hepatitis, the association was more evident at older ages, confirming the long lead time between infection and cancer occurrence, while for diabetes it was stronger (or restricted) to cases aged less than 60, suggesting a possible specific role of type I diabetes. While for hepatitis, cirrhosis, and blood transfusion this study offers further quantitative estimates of risk in a European population, the possible direct association with diabetes and protection by drug allergy were unexpected, lacked plausible biological or previous epidemiological support, and should be simply regarded as working hypotheses for further work.