There is increasing evidence that catecholestrogens may contribute to the development of breast cancer. Specifically, inactivation of catecholestrogens may prevent the genesis and arrest the progression of the disease. Catechol-O-methyltransferase (COMT), Glutathione S-transferase (GST) M1 and GSTP1 are responsible for the detoxification of catecholestrogens, and are polymorphic in the human population. In this study, a PCR-based restriction fragment length polymorphism analysis was performed to determine genotypes of the COMT, GSTM1 and GSTP1 genes. We investigated the relationship between the germline polymorphism of these genes and clinico-pathological characteristics in 140 patients with breast cancer. Among 73 patients with the low activity COMT allele, 49 (67%) had regional lymph node metastasis. On the other hand, only 27 (40%) of 67 patients without the low activity allele had lymph node metastasis. The COMT genotype was significantly associated with clinical stage and the extent of regional lymph node metastasis of breast cancer (P<0.05). However, polymorphisms of the GSTM1 and GSTP1 gene were not associated with clinico-pathological factors. Our findings suggest that the allele encoding for low activity COMT may contribute to the progression of breast cancer.