Background: CD166 is a glycoprotein of an immunoglobulin super family of adhesion molecules that has been associated with aggressive characteristics and high recurrence rate of tumors. Different odontogenic lesions exhibit considerable histological variation and different clinical behavior. In an attempt to clarify the mechanisms underlying this different behavior, the present study investigates the immunohistochemical expression of CD166 in these lesions. Material and Methods: In this study 69 formalin-fixed, paraffin embedded tissue blocks of odontogenic lesion consist of 15 unicystic ameloblastoma (UA), 17 solid ameloblastoma (SA), 18 keratocystic odontogenic tumors (KCOT), and 19 dentigerous cysts (DC) were reviewed by immunohistochemistry for CD166 staining. Results: In this study, CD166 immune staining was evident in all specimen groups except dentigerous cyst. In positive cases, protein localization was cytoplasmic and/or membranous. CD166 expression was seen in76.5% (13) of SA, 73.5% (11) of UA, and 66.7% (12) of KCOTs. Statistical analysis showed that CD166 expression levels were significantly higher in ameloblastoma (SA and UA) and KCOTs than dentigerous cyst (P<0.001), but there was no statistically significant difference between CD166 expression in the other groups (P>0.05). Conclusions: This data demonstrates that overexpression of CD166 may have a role in the pathogenesis of ameloblastoma and KCOT.