The association of the polymorphism in the genes of TNF-alpha, TNF-beta and IFN-gamma with breast cancer was investigated in the present study. There were no differences in the TNF-alpha and TNF-beta alleles and genotypes frequencies between breast cancer patients (n=223) and control subjects (n=267). The correlations between TNFA or TNFB alleles or genotypes and clinicopathological indices were also insignificant. However, the frequency of IFN-gamma+874 T/T genotype was significantly higher in breast cancer patients compared to those of controls (P<0.002; OR=2.03, 95% CI=1.28-3.2) which indicates that Iranian women carrying the IFN-gamma+874 T/T genotype may be exposed to an increased risk of breast cancer development.