Abstract: Small breast epithelial mucin (SBEM) is a kind of secreted protein expressed only in the mammary and salivary glands. It can be used as a tumor marker to detect the micro-metastasis in breast cancer and specific target in the treatment. The detection rate of SBEM is up to 51% in breast cancer tissue and that of SBEM-mRNA is 53.3% in the peripheral blood, which has a direct correlation with the TNM stage. The detection rate of micro-metastasis and sensitivity and accuracy in breast cancer can be improved by a combined assay with multiple genes, such as CK19-mRNA, PIP-mRNA, CEA, and MGA. The change of expression level could predict the curative effect of neo-adjuvant chemotherapy. SBEM-mRNA exhibits sensitivity and accuracy in the bone marrow micro-metastases of breast cancer, and has a direct correlation with the TNM stage. The detection of SBEM would have a better prospect for application because of its clear advantage in detecting the micro-metastasis of breast cancer and clinical supervision. The expression and correlation with the clinico-pathological features, the significance of the combined assay with multiple genes, as well as the value of clinical applications of SBEM-mRNA were reviewed in this paper.