Hepatocellular carcinoma (HCC) is one of the most common malignancies in certain parts of the world, particularly in Africa and Asia, but it is less commonly encountered in the United States. It is closely associated with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, and almost always develops in a cirrhotic liver. In non-cirrhotic livers, HCC is found in about 20% of asymptomatic carriers of HBV and rarely in patients taking androgenic-anabolic or oral contraceptive (OC) steroids. We report four patients, who developed HCC after prolonged use of OC steroids. Whether OC steroids act as mutagen or co-carcinogen in hepatocarcinogenesis is not clear. To exclude latent HCV and HBV infections which may occur in the absence of their serological markers, we employed polymerase chain reaction for the detection of HBV and HCV sequences in the tumor and non-tumorous liver tissue. Viral sequences of HBV and HCV were undetectable in all four cases. These findings suggest OC use as the only known risk factor in these cases and, therefore, strengthen its possible role in hepatocarcinogenesis.