Breast cancer (BC) is the second most common cancer, and mortality rates remain high among Brazilian women. However, the role of single nucleotide polymorphisms (SNPs) in one-carbon metabolism genes in breast cancer in Brazilian women is less clear. We aimed examine the association between the SNPs, in two genes in one-carbon metabolism alone and in cumulation, and the risk of breast cancer in an Brazilian population based case-control study of 257 breast cancer cases and 177 controls. Our hypothesis was woman who carries more risk genotypes has a higher susceptibility for developing breast cancer. Genotyping for MTHFR C677T and MTR A2756G polymorphisms were performed using polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP) method. Our results in population studied indicated that 677 CgtT and 2756 AgtG substitution does not appear to influence the risk of breast cancer. The cumulative effect was not observed with the OR being gradually elevated with increasing number of risk genotypes. However, larger studies are needed to further examine this interactions in this pathway and breast cancer risk in Brazilian women, as well in women of others nationalities.