To investigate the clinicopathological significance of cystatin M loss and to identify possible factors associated with cystatin M loss in breast cancer, we analyzed the expression status of five proteins (ER, PR, HER2, HER4, and cystatin M) and the hypermethylation of CST6 gene in a total of 292 breast cancer patients. The gene discussed is ERBB4; the disease is breast carcinoma.