Mucoepidermoid carcinoma (MEC) is defined as a malignant salivary gland tumor composed of mucous, intermediate, and epidermoid cells with cystic and solid growth patterns.1,2 Reflecting this definition, MEC often shows complex and confusing features cytologically and histoarchitecturally. The current consensus among pathologists is that molecular studies on mastermind like transcriptional coactivator 2 (MAML2) rearrangement is a prerequisite for the diagnosis of MEC, especially for diagnostically challenging cases and various histological subtypes.2 The 5th edition of the World Health Organization classification of head and neck tumors published in 2022 clearly adds MAML2 rearrangement as a desirable criterion.2

The present review comments on the histological subtypes of MEC and their differential diagnosis. In this context, we tentatively classified these MEC variants into three major categories: 1) MEC rich in metaplastic/morphologically transformed tumor cells (oncocytic, clear cell, and spindle cell variants); 2) MEC showing prominent stromal changes: sclerosing variant; and 3) MEC mimicking other well-known tumor entities (mucoacinar carcinoma, Warthin-like, and non-sebaceous lymphadenoma-like variants). For completeness, we also briefly refer to 4) MEC showing poorly described histological features.