Abstract: In this study investigations were made to detect the association of MTHFR C677T and A1298C polymorphisms in breast cancer patients, in the South Indian population. Eighty eight women patients with breast cancer and 95 healthy women as controls were included in the study after their consent to participate in this program. MTHFR gene polymorphisms were determined by the PCR-RFLP method. The allele frequencies of the MTHFR C677T were 27.84% in the breast cancer subjects and 19.47% in the controls. The allele frequencies of the MTHFR A1298C were 25.56% in the breast cancer subjects and 17.89% in the controls. Frequencies of MTHFR C677C, C677T and T677T were 47.9%, 44.8%, 7.1% in breast cancer patients and 63.2, 34.5 and 4.6% in the controls. Frequencies of MTHFR A1298A, A1298C and C1298C were 54.8, 40.8 and 5.1% in breast cancer patients and 66.9, 30.1 and 2.9% in the controls. When we compared the frequencies of C677T and T677T with C677C, A1298C and C1298C with A1298A, we found less significant association between specific MTHFR variants in breast cancer patients. Our findings suggest that MTHFR C677T and A1298C gene variants do not have a major influence on the susceptibility to breast cancer in south Indian population.