Breast cancer is a major problem among females all over the world. Despite apparent curative resection, subsequent development of metastatic spread presents a major clinical problem in about 30% of all breast cancer patients. The aim of this study was to investigate the clinical reliability of mammaglobin m-RNA (MAG m-RNA) as a marker of circulating cancer cells in breast cancer patients and to study the relevance of its expression in blood and expression of its protein in breast tissues, with the pathological parameters and its value in evaluating efficiency of treatment. This study was conducted on 48 breast cancer patients and 28 controls (10 healthy controls and 18 patient controls: 6 with fibroadenoma, 4 with uterine carcinoma, 4 with ovarian carcinoma and 4 with colon cancer). For histopathological study, the healthy control group included the normal breast tissue adjacent to fibroadenoma. All breast cancer patients were of the infiltrating ductal carcinoma type and 10 of them had associated areas of intraductal carcinoma. The patient group was classified into 26 patients with localized breast cancer and 22 patients with metastases (9 patients had axillary lymph node metastases and 13 patients had distant metastases). Breast cancer patients were reclassified according to the histologic grade into grade I (8 patients), grade II (26 patients) and grade III (14 patients). All individuals included in this study were subjected to detection of MAG m-RNA in circulating tumor cells in peripheral blood using nested PCR technique. Breast tissue expression of MAG was investigated using immunohistochemistry. Blood and tissue MAG expression were correlated with estrogen receptor and Ki-67 proliferation index. Circulating MAG m-RNA is a highly specific (100%) tumor marker. The detection rate was significantly associated with the histologic grades, ER positivity and low proliferative rate of tumors. The detection rate declines after receiving chemotherapy. Immunohistochemically, the pattern of expression of MAG in breast cancer tissues was characteristically different than that in non-cancer tissues (being diffuse cytoplasmic in the former and scattered in the latter). MAG overexpression in breast tissue was significantly higher in low grade tumors (I and II) than in high grade ones (III). The strong staining intensity was more frequently detected in low grade tumors. Also MAG expression in breast tissue was significantly correlated with ER positivity and low Ki- 67 proliferation index of the tumors. MAG is a promising specific tumor marker of breast cancer that could predict the prognosis of breast cancer and its response to hormonal treatment. [Turk J Cancer 2007;37(3):89-97]