The mammaglobin gene encodes a 10-kDa glycoprotein that is distantly related to a family of proteins that includes rat estramustine binding protein (EMBP)/prostatein and human Clara cell 10-kDa protein (CC10)/uteroglobin. Among normal adult tissues, mammaglobin mRNA expression has been detected only in the mammary gland. As an initial step to determine mammaglobin's clinical utility as a breast tumor marker, we evaluated the frequency and specificity with which mammaglobin expression could be detected in primary breast tumors, metastatic breast tumors, and breast tumor cells present in the peripheral circulation. Approximately 80% of all primary and metastatic breast tumors examined were strongly immunopositive for mammaglobin protein, and staining was independent of tumor grade. Among peripheral stem cell collections from breast cancer patients, mammaglobin mRNA could be detected in 60% of cases. Recent work has identified the secreted mammaglobin protein in the sera of some breast cancer patients using both Western blot and ELISA. This study demonstrates that the detection of mammaglobin protein and mRNA in clinical samples may be a useful marker for primary, metastatic, and occult breast cancer.