This report describes the immunocytochemical localization of a human basal- or myoepithelial-specific anti-keratin antibody in benign and malignant breast disease. Reactivity patterns with this antibody have demonstrated the lack of myoepithelial or basal epithelial participation in most benign breast specimens examined including those displaying cystic disease, fibrosis, or hyperplasia. However, in specimens of sclerosing adenosis, strong reactivity with the majority of cells in most ducts suggests a major participation of the myoepithelial cell type. Analysis of 118 breast carcinoma specimens has demonstrated strong, homogeneous reactivity in 4% of the specimens, suggesting a role for the basal epithelial cell in malignancy of the human mammary gland and implications for the prognosis of such tumors. Antigenic characterization of the malignant and benign mammary specimens which are uniformly reactive with the antibody has demonstrated the presence of a 51 kd keratin polypeptide not found in the non-reactive specimens.