OBJECTIVE: This study aimed to assess the expression of invadopodia-related proteins in mucoepidermoid carcinoma and their influence on this tumor's invasiveness. MATERIAL AND METHODS: Twenty-seven mucoepidermoid carcinoma grading samples were evaluated for the expression of Tks4, Tks5, cortactin, and MT1-MMP and compared to 10 control samples of normal-looking salivary glands by immunohistochemistry. For in vitro analysis, immunofluorescence identified the expression of invadopodia-related proteins in the mucoepidermoid carcinoma cell line. Invadopodia formation and invasion assays were performed after silencing of Tks4 and Tks5 to evaluate invasiveness. RESULTS: The invadopodia-related proteins were expressed significantly higher in mucoepidermoid carcinoma samples when compared to the control group. Positive expression of these proteins was identified in the mucoepidermoid carcinoma cell line. Knockdown of Tks4 and Tks5 reduced both gelatin degradation and invadopodia activity in mucoepidermoid carcinoma cell lines. CONCLUSION: Our results suggest that mucoepidermoid carcinoma behavior can be mediated by the expression of invadopodia-related proteins. Tks4 and Tks5 play a role in the invasiveness of mucoepidermoid carcinoma, mediated by invadopodia.