The earlier reports on the association between the Ile to Val polymorphism at codon 655 of HER-2 and susceptibility to breast cancer has not been found to hold true for all ethnic populations. Two hundred and four cases and 138 controls were collected to investigate the association of HER-2 Ile655Val polymorphism with the risk of breast cancer development and progression in Iranian population. This association was not found to be significant in the present study (OR = 1.16, 95% CI: 0.67-2.03). The association between HER-2 genotypes frequency and clinicopathological data was also insignificant, suggesting that the HER-2 polymorphism at codon 655 is unlikely to be a susceptibility locus in Iranian patients with breast cancer.