Epithelial membrane protein 3 (EMP3) is a trans-membrane signaling molecule with important roles in the regulation of apoptosis, differentiation and invasion of cancer cells, but the detailed is largely still unknown. We analyzed the mRNA levels and methylation statuses of EMP3 in 63 primary breast carcinomas and assessed their correlations with clinicopathologic variables. The expression of EMP3 mRNA in primary breast carcinomas was significantly higher than the expression of 20 normal breast tissues (p<10-7). EMP3 overexpression in breast carcinomas was significantly related to histological grade III (p=3.9×10-7), lymph node metastasis (p=0.003), and strong Her-2 expression (p=3.3×10-6). Hypermethylation frequencies of EMP3 were detected in 36.5% of breast carcinomas by methylation-specific polymerase chain reaction. However, no significant correlations were found between methylation status of EMP3 and mRNA expression levels as well as other clinical parameters. In conclusion, EMP3 may be a novel marker of tumor aggressiveness. Overexpression of EMP3 in primary breast carcinoma is not associated with DNA methylation.