Objective: To investigate the immunohistochemical expression of SOX2 among the studied cases of ameloblastoma and odontogenic keratocyst in order to show if it correlates to the biological behavior of those odontogenic lesions. Materials and Methods: The study was carried out on 30 histo-pathologically confirmed cases of (15 ameloblastomas and 15 odontogenic keratocysts). These blocks were collected from archived files of the Department of Oral Pathology, Faculty of Dentistry, Mansoura University. Sections were subjected to Immunohistochemical staining by SOX2 according to a standard protocol. Results: OKCs showed higher expression of SOX2 than Ab in all epithelial layers not confined to the basal layer only with a p-value <0.001. The reaction in recurrent ameloblastomas was significantly higher than in non-recurrent cases (p= 0.036). Conclusions: SOX2 is a reliable marker for identifying the stem cell population in odontogenic lesions. Targeted therapies may be designed against these SC populations to render more effective treatment and prevent recurrence.