Chronic hepatitis C and B are the main causes of hepatocellular carcinoma (HCC) worldwide. Little is known about the etiology of HCC in Germany which is regarded as a low-prevalence area for viral hepatitis C (HCV) and B (HBV). To assess the etiologic factors of HCC in Germany we have retrospectively analyzed the records of 100 consecutive patients with hepatocellular carcinoma in our clinic. HCC-patients with documented status on HCV/HBV-infection and daily alcohol intake (n = 55) had HCV antibodies in 53%, HBs-Ag in 20%, isolated chronic alcohol abuse in 11% and genetic hemochromatosis in 2%. In 13% of the HCC-patients no risk factor could be identified. Coinfections with HCV and HBV were not observed. Liver cirrhosis was present in 90% of the HCC-patients. In histologically confirmed HCC (n = 71) serum alpha-fetoprotein level was normal (< 8.5 ng/ml) in 20%, moderately elevated (8.5-300 ng/ml) in 48% and considerably elevated (> 300 ng/ml) in 32% of the patients. Only 31% of all patients presented with small single lesions (< or = 5 cm) without evidence for extrahepatic metastases or portal vein thrombosis. Only 30% of the HCC-patients could be treated with a curative intention (28 hepatic resections, one orthotopic liver transplantation). Patients who underwent resection had cumulative 6-month, 1-year, 2-year and 3-year survival rates of 83.8%, 65.9%, 54.3% and 24.8% respectively. Median survival time after resection was 24.8 months compared with 5.8 months in symptomatically treated patients with unresectable HCC (n = 39). Patients with hepatitis C-associated HCC were significantly older than patients with hepatitis B-associated HCC (mean values: 63.2 vs. 54.2 years). Frequency of cirrhosis, tumor stage, alpha-fetoprotein level and prognosis did not differ between groups. In conclusion hepatocellular carcinoma was predominantly associated with chronic HCV-infection. Most patients presented with normal or moderately elevated serum AFP-levels. Prognosis was poor even after hepatic resection.