CD166 is a glycoprotein of immunoglobulin superfamily of adhesion molecules which is overexpressed in many tumors. However, no published literature was found concerning CD166 expression in salivary gland tumor. The purpose of this study was to examine the CD166 expression in the salivary gland tumor by an immunohistochemical approach, to examine the clinical implication of this marker in the prognosis and diagnosis of the salivary gland tumor. In this study, 45 samples of salivary tumors from Khalili Hospital archive including 15 cases of pleomorphic adenoma, 16 cases of mucoepidermoid carcinoma, 14 cases of adenoid cystic carcinoma, and 15 normal salivary glands were selected for immunohistochemistry (IHC) method staining for CD166. CD166 immunoreactivity in malignant tumors (adenoid cystic carcinoma (ACC) and mucoepidermoid carcinoma (MEC)) (56.7 ± 14.05) was significantly higher than that of pleomorphic adenoma (PA) (34.3 ± 17.07) (P < 0.000) and higher in the PA than normal salivary gland (13.2 ± 12.1) (P = 0.001). CD166 expression was significantly higher in the high-grade tumors (90.3 ± 11.07) compared to low-grade (65.11 ± 27.08) malignant tumors (P = 0.002). CD166 expression showed a significant association with tumor size and the clinical stage (P < 0.001). In conclusion, an overexpression of CD166 was detected in the benign and malignant salivary gland tumors and its expression in the malignant tumor was associated with the aggressive behavior and tumor progression. For this reason, CD166 may be one of the potential biomarkers for predicting tumor behavior in the prognosis of this disease.