Abstract: Abstract　Objective: To investigate the expression and significance of both seven in absentia homology 2 ( SIAH2 ) and B-cell lymphoma 2 ( Bcl-2 ) in normal mammary glands and invasive ductal carcinoma ( IDC ) and to discuss the role and correlation between them during breast carcinogenesis. Methods: SIAH2 and Bcl-2 expression were determined using immunohistochemical SP method, and the relationship between the SIAH2 and Bcl-2 protein expression and the clinical pathologic features were analyzed. Western blot analysis was conducted to determine the SIAH2 and Bcl-2 expression. Results: SIAH2 and Bcl-2 expression significantly increased during breast carcinogenesis and were correlated with histologic grade, as well as estrogen and progesterone receptor expression. The immunohistochemistry results showed that there was an increasing tendency in positive expression rate of SIAH2 and Bcl-2 in normal breast tissues ( 8.7% and 17.4%, respectively ) to IDC (7 5% and 72.5%, respectively ). Spearman's correlation revealed that SIAH2 expression was significantly correlated with Bcl-2 expression in the 80 breast cancer specimens ( P < 0.001, rs = 0.485 ). Western blot analysis showed that SIAH2 and Bcl-2 protein expression were significantly higher in breast tumor tissues compared with those in paraneoplastic tissues, which was the same compared with the protein expression among the human breast cancer MDA-MB-435S and MCF-7 cell lines, and the normal breast epithelial MCF-10A cell line. Conclusion: Our results indicated that both SIAH2 and Bcl-2 are involved in breast cancer and may imply coordination in breast tumorigenesis.