There is compelling evidence to suggest that catecholestrogens may play a role in the development of breast cancer. Particularly, inactivation of catecholestrogens may prevent the genesis and arrest the development of breast cancer. Catechol-O-methyltransferase (COMT) is polymorphic and responsible for the detoxification of catecholestrogens. In the present study, we examined what role COMT gene polymorphisms may play in the development of breast cancer in a case-control study of 130 sporadic unrelated premenopausal Turkish breast cancer patients with 233 unrelated healthy controls. The frequency of COMT-L allele was more significantly represented in the breast cancer cases (48.08%) than in the controls (38.20%). The genotype frequencies of COMT-HH, HL and LL were 25.4, 53.1 and 21.5% in the breast cancer subjects and 26.6, 62.7 and 10.7% in the controls respectively. In conclusion, the COMT-L allele and COMT-LL genotype are genetic risk factors for sporadic breast cancer in premenopausal Turkish women.