We determined whether immunostaining for mucins could provide a better characterization of salivary gland mucoepidermoid carcinoma (MEC). We investigated 63 MECs by immunohistochemistry for MUC1, MUC2, MUC4, and MUC5AC. Mucin expressing cell types and labeling patterns were recorded. The results were compared with microscopic grade, tumor-associated lymphoid infiltrate, mucin expression in surrounding salivary glands, clinical features, and outcome. MUC1 and MUC4 labeled the apical membrane of glandular tumor cells and the entire membrane of intermediate, clear, and epidermoid tumor cells. MUC2 and MUC5AC were expressed in the cytoplasm of glandular, mucous, and intermediate tumor cells. In contrast to MUC1, MUC4 expression decreased with tumor grade (P < 0.01). Unlike MUC2, MUC5AC was expressed in more than 50% of high-grade tumors, including 2 cases that were not stained with Alcian blue. MUC1 and MUC5AC were associated with tumor-associated lymphoid infiltrates (P < 0.05), but not with tumor-associated lymphoid follicles. The proportions of tumors expressing mucins were 71% for MUC1, 21% for MUC2, 79% for MUC4, and 68% for MUC5AC. MUC1 and MUC5AC were more frequently expressed in tumors than in surrounding glands (P < 0.0001). MUC1 expression correlated with shorter progression-free survival (P < 0.05). In conclusion, mucin expression in MEC differs from that in salivary glands. Intermediate cells express MUC1 and MUC4 all along their cell surface and MUC2 and MUC5AC in their cytoplasm. Staining for MUC5AC in high-grade tumors can be helpful for distinguishing high-grade MEC from squamous cell carcinoma. While MUC4 is related to tumor differentiation, MUC1 expression indicates a worse prognosis.