MicroRNAs (miR) are small noncoding RNAs that are predicted to regulate up to 30% of protein-encoding genes. miR maturation requires functional microRNA machinery, including the Dicer protein. We review our experience with mucoepidermoid carcinoma (MEC) and characterize the prognostic value of Dicer expression. Expression of Dicer was assessed in 78 MEC by immunohistochemistry. Dicer expression was scored semiquantitatively and relative to the internal controls: large excretory/striated ducts or basal/parabasal layers of normal squamous epithelium (mucosa). Dicer scores were then correlated with clinical and pathologic parameters. Dicer over- and/or under-expression were more commonly seen in high-grade MEC (83%) than in low/intermediate grade MEC (35%; p=0.002) and in stage III/IV MEC (80%) than in stage I/II MEC (41%; p=0.04). Abnormal Dicer expression correlates with high-grade and advanced stage, acting as a univariate predictor of poor disease-specific survival (DSS) in MEC. Age and stage were independent predictors of poor DSS on multivariate analysis. Abnormal immunoexpression of Dicer in aggressive MEC suggests a role for miR and miR machinery in tumor progression.