Thirty-one salivary gland epithelial-myoepithelial carcinomas from 26 patients were studied by DNA flow cytometry, and immunostaining for Ki-67 and HER-2/neu oncogene product. The results were correlated with clinicopathologic factors and patient outcome. The tumor most commonly involved the parotid gland, and mainly affected patients in their 6th to 8th decades. The clinical course was characterized by a high incidence of local recurrence (50%) and not infrequent distant metastasis (25%). None of the patients in this cohort died of disease. DNA content analysis revealed 21 neoplasms with DNA diploidy and 5 tumors with DNA aneuploidy; all aneuploid cases were near-diploid (hyperdiploidy) and showed low proliferative activity. All aneuploid and 60% of the diploid neoplasms developed recurrences and/or metastases. Immunohistochemical analysis of Ki-67 proliferation markers also showed low overall growth fractions. Interestingly, Ki-67 immunoreactivity was largely restricted to myoepithelial cells, suggesting a central role for this cell in the development of these tumors. HER-2/neu oncogene analysis failed to demonstrate overexpression in any of the tumors examined. This study indicates that epithelial-myoepithelial carcinoma is a low grade malignant neoplasm with a high propensity for recurrence. HER-2/neu oncogene and Ki-67 offer no additional advantages over current factors in the biologic evaluation of these neoplasms. DNA aneuploidy may allow for the identification of a subset of tumors that is more prone to recurrence and metastasis, but further studies with extended follow-up are needed.