Background: Aberrant methylation of cytosine-guanine dinucleotide islands leads to inactivation of tumor suppressor genes in breast cancer. Tumor suppressor genes are unmethylated in normal tissue and often become hypermethylated during tumor formation, leading to gene silencing. We investigated the association between E-cadherin (CDH1) and estrogen receptor-α (ESRα) gene promoter methylation and major clinical and pathological features of breast cancer in Iranian women. Methods: DNA was extracted from 67 primary breast tumors and gene promoter methylation was analyzed by methylation-specific polymerase chain reaction method. Results: Fifty percent of the samples showed aberrant methylation in at least one of the two tested loci. We detected CDH1 hypermethylation in 41% of invasive tumors and receptor-α gene hypermethylation in 18% of invasive tumor samples. We found no association between CDH1 and receptor-α gene hypermethylation (P=0.45). There was a correlation between hypermethylation of CDH1 locus and tumor size ≥5 cm (P=0.019). Conclusion: Our data suggest that the malignant progression of human ductal and lobular breast carcinoma in Iranian women involves a heterogeneous pattern of cytosine-guanine dinucleotide island hypermethylation of the CDH1 gene.