The seven signal transducer and activator of transcription (STAT) molecules are effectors of hormonal or cytokine stimulation through receptors. STAT 5a, isolated from prolactin-stimulated mammary cells, contributes to normal proliferation and is essential for mammary gland differentiation. Using a monoclonal antibody, we tested 100 formalin-fixed, paraffin-embedded breast tissues representing everything from simple hyperplasia to invasive carcinoma for the expression of STAT 5a in comparison to normal breast epithelial cells. Immunohistochemical analysis was performed following heat treatment in a pressure cooker. STAT 5a was found in endothelial cells, adipocytes, and leukocytes as well as in the cytoplasm and nucleus of normal epithelial cells, usual ductal hyperplasia, and benign lesions such as fibroadenoma. Myoepithelial cells and stromal fibroblasts failed to demonstrate any STAT 5a in addition to most atypical proliferations including in situ and invasive carcinomas. A few examples of lobular intraepithelial neoplasia and invasive carcinoma demonstrated some reactivity, albeit comparatively reduced. The absence of STAT 5a in the abnormal breast epithelial cells may indicate a defect contributory to the abnormal state.