Abstract The expression of cyclooxygenase 2 (COX-2) is induced by growth factors, tumor promoters, and cytokines. It is correlated with carcinogenesis and apoptosis inhibition. This study was designed to investigate the expression of COX-2 and BCl-2 and to correlate their expressions with the clinicopathologic features in the mucoepidermoid carcinoma (MEC). The expression of COX-2 and BCl-2 proteins was investigated in 16 archival tumor tissues of MEC using the streptavidin-biotin complex technique. Clinical information was obtained through the computerized retrospective database from the tumor registry between 2001 and 2007. It revealed that grading system of MEC did not correlate with the presence or absence of node metastasis. The expression of COX-2 and BCl-2 was variably expressed in all the examined specimens. COX-2 and BCl-2 immunoreactivity was observed mainly in the cytoplasm of neoplastic cells. As regard the clinicopathologic parameters, there was no significant difference in expression rates of COX-2 in patients among age, sex, and MEC grades ( P > .05). However, the expression of COX-2 in node-positive tumors was significantly higher than that of node-negative tumors ( P = .001). For BCL-2 expression, there was no significant difference in expression rates of BCl-2 in patients among age, sex, site, clinical stage, and lymph node metastasis ( P > .05), whereas a high significant difference was observed between BCl-2 staining index and MEC grades ( P = .027). Moreover, there is a positive correlation between COX-2 expression and BCL-2 staining index ( P = .000). COX-2 is a good predictor for lymph node metastasis as well as ideal therapeutic target for the prevention or treatment of MEC. BCl-2 and COX-2 are potentially useful prognostic markers for MEC.