Breast cancer is the most common cancer among women in the world. In Iran, the incidence of breast canceris on the increase. We here studied the association of rs1219648 in FGFR2 and rs1042522 in TP53 and theirinteraction in development of early onset sporadic breast cancer in Iranian Azeri population to evaluate epistaticeffects on the risk of mammary neoplasia. We genotyped the two polymorphisms in 100 women with early onsetbreast cancer and 100 healthy women by PCR-RFLP. Allele frequency differences were tested using chi2-test with95% confident intervals. Our results indicated a statistically significant association (p<0.05) between rs1219648,but not rs1042522, and risk of breast cancer. We also found that the combination of FGFR2 major genotypeand TP53 hetero genotype had protective effects against breast cancer , while the hetero allele of FGFR2 incombination with the minor genotype of TP53 was associated with a high risk. This study revealed an importantcrosstalk between two polymorphisms in FGFR2 and TP53 in development of breast cancer. These candidatesrisk variants should be further evaluated in studies with a larger sample size.