Breast cancer is a complex disease with both genetic and environmental factors involved in its etiology. An important role of polymorphisms in genes involved in DNA repair has been reported related to breast cancer risk. We conducted a case-control study in order to investigate the association of RAD51 135G>C and TP53 Arg72Pro polymorphisms with breast cancer in Serbian women.48 BRCA negative women with breast cancer and family history of breast/ovarian cancer (hereditary group), 107 women with breast cancer but without family history of the disease (sporadic group) and 114 healthy women without a history of the disease (control group) were included. Restriction fragment length polymorphism was used for genotyping. Genotype and allelic frequencies, the odds ratio (OR) and the 95 % confidence interval (CI) were calculated as an estimate of relative risk. The Hardy-Weinberg equilibrium was tested using χ(2) test. Significance was considered for p < 0.05. RAD51 135G>C showed statistically significant association of CC genotype and increased breast cancer risk (OR 10.28, 95 % CI 1.12-94.5) in hereditary group of patients compared to the control group. Regarding the TP53 Arg72Pro, we showed statistical significance for ProPro + ProArg comparing to ArgArg (OR 2.34, 95 %, CI 1.17-4.70) in hereditary compared to sporadic group. RAD51 135G>C contributes to hereditary breast cancer in Serbian population, with CC genotype as a risk factor. We also found that carriers of Pro allele of TP53 codon 72 is related to hereditary cancer comparing to sporadic one, which indicates it as a potential risk factor for hereditary form of disease.