Background: Odontogenic keratocyst (OKC) is one of odontogenic lesions which has been recently classified as a developmental cyst in last WHO odotogenic classification 2017, despite of its clinical aggressiveness and relative rate of recurrence. Aim : The aim of the current work was to assess and compare Odontogenic keratocyst with both ameloblastoma (AM) and radicular cyst (RC) in relation to immunohistochemical expression of BCl2 and CD138 . Method: This is a retrospective study included 15 cases of Odontogenic keratocyst, 20 cases of ameloblastoma, and 15 cases of radicular cyst. Immunohistochemical technique was applied to detect and compare BCL2 & CD138 expression in these lesions. Results: For BCL2, (86.6 %) of odontogenic keratocyst cases and all studied ameloblastoma cases (100%) were positive for bcl-2 without significant statistically correlation (p>0.05).At the same time odontogenic keratocyst were significantly correlated with radicular cysts which were completely negative to Bcl-2 (