Six cases of adenoid cystic carcinoma (ACC) of the breast were reviewed. Immunohistochemical studies were carried out for actin, S-100 protein, EMA, keratin, CEA, vimentin, NSE, alpha-lactalbumin, and lysozyme. Fine needle aspiration biopsy smears of five patients were also reexamined. Patients were treated by tumorectomy, quadrantectomy, or modified radical mastectomy. Axillary dissection was carried out in five cases, with negative lymph nodes in all. Five patients are alive without evidence of disease from 1 year 10 months to 13 years 4 months following surgery. One patient died 7 1/4 years after mastectomy, without evidence of disease. Histologically, a diagnostic biphasic cellular pattern was seen in all cases. In addition, several unusual features were encountered in some cases: squamous metaplasia, stromal myxoid pseudocartilaginous foci, and well-formed neoplastic ducts. Actin and/or S-100 protein were variably positive in all cases. The reaction was usually present in occasional basaloid cells predominantly at the periphery of neoplastic structures. Keratin, EMA, and CEA immunostaining disclosed ductal type cells in all cases. Vimentin was positive in four cases, usually in many basaloid cells. Aspiration cytology was suspicious in two cases and yielded a definitive diagnosis of ACC in three cases. Cytologic diagnosis was based on cellular morphology and on the presence of characteristic globoid structures. Immunohistochemical results show that in ACC dual myoepithelial-ductal differentiation occurs but is relatively limited. Most of the tumor cells are not differentiated ("indifferent" cells) and often express strong vimentin positivity. Such cells are regarded as precursor cells for either differentiated element. Unusual metaplastic changes in breast ACC suggest a possible relation with pleomorphic adenoma-type tumors, and this might be of prognostic significance.