Pleomorphic adenomas of the breast (PAB) are uncommon tumors. We studied the clinicopathologic features of 10 cases of PAB, seven of which were assessed immunohistochemically. Nine patients were women, with a median age at diagnosis of 65 years. Eight patients presented with a palpable mass; two had a nipple discharge. Nine of the tumors were periareolar. The latter epidemiologic findings, coupled with histologic observations, appeared to indicate a preferential origin for PAB within large intramammary ducts. These neoplasms histologically resemble their analogues in salivary glands. Moreover, a gradual histologic transition between different morphologic areas in PAB, especially between mesenchymal and epithelial regions, supported the contention that the neoplasm arises from a single cell type capable of divergent differentiation and thus should not be considered a "mixed" tumor. This contention was further substantiated by immunohistochemical findings, in which three intermediate filaments (cytokeratin, vimentin, and glial fibrillary acidic protein) and muscle-specific actin were expressed conjointly in tumor cells with a variety of morphologic appearances. In addition, cells differentiating along mesenchymal lines by conventional microscopy were found to express epithelial membrane antigen or gross cystic disease fluid protein-15 in five cases. The benign nature of PAB was supported by a lack of metastases in this series during a median follow-up period of 4.9 years. However, one lesion recurred locally. Regarding therapy, we believe that PAB can be excised successfully with only a narrow circumferential margin of uninvolved breast.