The preclinical safety assessment of cyproterone acetate (CPA) with regard to liver tumorigenesis was based on tumorigenicity studies, which revealed no mutagenic potential. Recently, in vitro studies on the formation of adducts and the enhancement of DNA repair synthesis with CPA have been published. These results are not unique to CPA, and the role of adducts and increased DNA synthesis in mutagenesis is still not clear. Dose-related hepatic toxicity has been reported with the prolonged use of CPA. An active surveillance study of patients taking long term CPA treatment has shown no correlation between the duration of CPA treatment and the prevalence of liver enzyme elevations. In a multicentre surveillance study of long term CPA use in 2506 patients included so far, not a single case of hepatocellular carcinoma has been observed. These findings do not support the theory of an elevated risk of hepatocellular carcinoma as a result of CPA treatment. In conclusion, there have been no observations which could point to an increased risk of proliferative liver change as a result of CPA treatment.