PTEN/MMAC1/TEP1 encodes a tumor suppressor protein, which regulates cell cycle progression, translation, and apoptosis by blocking the activation of Akt/PKB. The loss of PTEN function increases cell survival and induces tumor invasion. In this study, PTEN promoter status and its correlation with genetic and pathologic parameters were analyzed in genomic DNA from Iranian patients with breast cancer. DNA methylation patterns in the CpG islands were determined by a methylation-specific PCR (MSP) assay. PTEN promoter methylation was found to be present in 37 of 53(70%) tumor tissues and none in 20 normal counterparts. Moreover, promoter methylation was found in patients with heterozygote mutation in the PTEN gene. The pathological history of cancerous tissue sections showed that PTEN gene could be inactivated at the stages III and IV in sporadic breast cancer. These findings suggested that promoter hypermethylation of PTEN might contribute to the progression of sporadic breast cancer in human.