Pleomorphic adenoma (or benign mixed tumor) of the breast is a rare benign neoplasm that might be misinterpreted both clinically and pathologically as a malignant tumor. The authors present an additional case of this unusual lesion studied by immunohistochemistry, electron microscopy, and flow cytometry. A 77-year-old white woman presented with a 2-cm, nontender, mobile, calcified, right subareolar mass suggestive of a fibroadenoma. Microscopically, the tumor resembled a pleomorphic adenoma occurring in salivary glands. Positive immunostaining for S-100 protein, cytokeratin, and muscle-specific actin, as well as the ultrastructural presence of intermediate filaments with dense bodies and intercellular junctions, supported the predominant myoepithelial cell differentiation within the tumor, whereas the epithelial cell component stained only with cytokeratin and contained formed lumina with surface microvilli. The DNA pattern was diploid. The patient is alive and well 14 months after surgery. The authors' findings confirm that pleomorphic adenoma of the breast is a benign neoplasm in which myoepithelial cell proliferation plays a major role in tumorigenesis.