BACKGROUND: Cancer stem cells (CSCs) are thought to be a critical subpopulation in tumor development, progression, metastasis and recurrence. The identification of these cells is an initial step in understanding their role in oncogenesis and in seeking valuable markers for diagnosis or development of targeted therapeutics. This study aimed to evaluate the immunohistochemically the expression of CD133 in different histopathological grades of OSCC and determine the clinical significance of CD133 in the studied OSCC cases. Methods:Immunohistochemical staining for CD133 was performed in 50 archived histopathology specimens; the scoring of CD133 staining was carried out based on two parameters:1) staining intensity and 2) percent of tumor cells. Tissue was considered positive for CD133 if the score located within 1+, 2+ and 3+. Results:CD133 expression was highly variable amongst different samples, the staining of CD133 was detectable in less than 5% of tumor cells in 10 (20.0%) cases. No correlation was observed with age, sex, site, shape, site of lymph node, distant metastasis and recurrence, while a significant correlation was observed with tumor stages, tumor size and histopathological grades. Conclusions:Expression of CD133 was detectable in the majority of OSCC samples and correlated significantly with tumor stages, tumor size and histopathological grades. From these findings, we can conclude that CD133 might play a role in OSCC progression and could be considered as a prognostic indicator in OSCC.