The MECT1/MAML2 translocation is identified in a large proportion of mucoepidermoid carcinomas (MEC) of the salivary gland and is an emerging favorable prognosticator. However, there are conflicting data on this translocation's specificity, restriction to low/intermediate MEC, and strength as a prognosticator. We present our experience with the MECT1/MAML2 translocation in a large cohort of MECs to address these issues. We analyzed 55 salivary MEC and 36 potential MEC mimics (24 Warthin tumors, 5 oncocytomas, 3 squamous cell carcinomas, 2 squamoid salivary duct carcinomas, 1 lymphoepithelial cyst, 1 Schneiderian carcinoma ex papilloma) for presence of the MECT1/MAML2 translocation by fluorescent in-situ hybridization (FISH) and real-time RT-PCR. Overall, MECT1/MAML2 translocation was present in 36/55 (66%) of MEC whereas all 36 non-MEC were negative for translocation. Low or intermediate-grade MEC had a higher frequency of translocation (75%) than high-grade MEC (46%) (P=0.039). Translocation positive cases had a better disease-specific survival (log rank P=0.026) although 2 patients still died of disease. Within high-grade MEC, MECT1/MAML2 positive tumors had lower rates of anaplasia (P=0.001), and mitotic counts (P=0.012). Thus, MECT1/MAML2 translocation is highly specific for MEC and imparts a better prognosis. However, it is frequent even within high-grade MEC and can be seen in lethal cases suggesting that translocation status should not supersede conventional parameters. There are 2 distinct subgroups within high-grade MEC, and the translocation negative tumors may actually be more appropriately categorized as another tumor type (such as adenosquamous carcinoma).