Breast cancer (BC) is one of the most common causes of death among women, and second in Iran. The objectives of this study were to determine the frequency of RAD51 G/C polymorphism in patients with breast cancer. We evaluated these polymorphisms and effects on the breast cancer risk association in a Iranian sporadic population-based case-control study of 294 breast cancer cases and 315 controls using a PCR-RFLP-based assay. Analyses of affected and controls show that homozygote genotype RAD51 GG has the highest frequency in both groups (33.3 in patients and 41.4 in control group). Genotype RAD51 GG most risk factor were in our population: [CC/GC odds ratio, 0.364 (95 % confidence interval; CI, 0.168-0.788) p = 0.009, CC/GG odds ratio, 0.828 (95 % CI, 0.411-1.668) p = 0.596], GG/GC odds ratio, 2.276 (95 % CI, 1.497-3.460) p = 0.001]. There was a significant association of breast cancer risk with RAD51 GG and CC polymorphism.