Polymorphic variations may affect the rate of gene transcription, the stability of the mRNA, or the quantity and activity of the resulting protein. In this study We evaluated the association between the interleukin-1B C-31T, catechol-O-methyltransferase Val158Met, and thymidylate synthase (TS) 1494del6 polymorphisms and breast cancer. Each genetic polymorphism was investigated by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis. No significant difference in either the genotype distribution or the allelic frequencies of the IL-1B and C : OMT gene polymorphisms was observed between the patient and control groups. For the TS 1494del6 polymorphism a significant difference was observed for both the genotypes (P=0.01) and the allele frequencies (P=0.0097), indicating a decreased risk associated with the variant allele. Our data do not provide evidence for an association between the polymorphic variants of the IL-1B and COMT genes and breast cancer risk. On the other hand, the TS 1494del6 polymorphism is associated with a significantly lower risk of breast cancer and may be a potential genetic marker.