Background and Aim: Mucoepidermoid carcinoma (MEC) is the most common malignant neoplasm of the salivary glands with complex histopathologic features and clinical behavior. The aim of this study was to evaluate the clinicopathologic significance of p63, Maspin and matrix metalloproteinase (MMP)-2 expression in MEC. Materials and Methods: In this retrospective study, immunohistochemical staining was performed to detect the expression of p63, Maspin and MMP-2 in 35 cases of MEC. In addition, to detect the presence of myoepithelial differentiation, smooth muscle actin (SMA) staining was performed. Data were analyzed using non-parametric tests. Results: P63 expression, intensity of staining for p63 and MMP-2 total score showed significant correlations with histologic grade (P=0.008, P=0.035 and P=0.003, respectively). The association between p63 expression and MMP-2 total score was significant (P=0.033). P63 positive cases did not express SMA. Conclusion: Findings suggest that p63 and MMP-2 may be useful prognostic indicators in MEC. MEC is devoid of myoepithelial cells.