Abstract: Objective: To investigate the relationship between COMT genetic polymorphisms and the development and prognosis of breast cancer. Methods: A G/A (Val/Met) polymorphism in codon 158 in exon 4 of COMT was analyzed using polymerase chain reaction- restriction fragment length polymorphism (PCR- RFLP) in 200 cases with breast cancer and 100 samples of normal breast tissue. The expression of ER, PR, p53 and CerbB- 2 was detected in the samples using immunohistochemistry. The difference in genotypic distribution frequency between the groups, the correlation between the genotypes and the factors related to prognosis were analyzed. Results: The incidence of homozygous and variant genotypes in breast cancer was significantly higher than in the controls (P=0.026 7). The proportion of variant genotype increased as clinical stage (P=0.008 2) and histological grades (P=0.014 6)advanced, as well as with increased numbers of lymph node metastases (P=0.038 7). In the ER positive group, there was a more significant correlation between the COMT genotypes and the clinical stage (P=0.000 4), histological stages (P=0.011 6) and lymph node metastasis (P=0.000 8). Conclusion: The variant genotype (Met/Met) is associated with breast cancer risk. In patients with breast cancer there is a correlation between the low activity COMT allele (COMT- LL and COMT- HL) and some factors indicating poor prognosis, including more lymph node metastases as well as a more advanced clinical stage and histological grouping.