INTRODUCTION: Odontogenic tumors (OTs) constitute a wide range of lesions derived from the tooth forming apparatus and its remnants. These tumors are generally benign, yet some are aggressive and have locally invasive behavior with a high rate of recurrence and some are malignant. Tumor stem cells (TSCs) are a unique subpopulation of cells that possess the ability to initiate a neoplasm and sustain self-renewal. Epithelial stem cell (ESC) markers such as sex-determining region Y (SRY)-box 2 (SOX2) are capable of identifying these stem cells which are expressed during the early stages of tooth development. OBJECTIVES: To evaluate immunohistochemically the expression of the stem cell proliferating marker SOX2 in benign and malignant epithelial odontogenic tumors. MATERIAL AND METHODS: Immunohistochemical (IHC) study using the SOX2 antibody was done on 30 surgical specimens of benign and malignant epithelial OTs as study group and 5 normal tooth germ tissues as a control group. RESULTS: Malignant OTs biopsies showed intense immune-reactivity to SOX2, while aggressive benign OTs showed medium immunereactivity with variable intensity. Totally benign tumors were immune-negative. The IHC staining intensity was directly proportional to the state of malignancy of odontogenic tumors. The difference in the expression of SOX2 in malignant and benign OTs was statistically significant. However, the difference in the expression of SOX2 in OTs and control group was not statistically significant in mean of area percent, while it was statistically significant in mean of optical density. CONCLUSIONS: SOX2 is highly expressed in malignant OTs biopsies. Medium immune-reactivity with variable intensities is seen in aggressive benign OTs.