Background: Ameloblastoma is a common benign aggressive odontogenic tumor with a tendency for high recurrence rate. Ameloblastic Carcinoma is the malignant counterpart of Ameloblastoma. However, they are usually difficult to be distinguished from one another. Therefore, using Immunohistochemical markers might be beneficial for diagnosing them accurately.Objective: Evaluation of SOX2 and GPC3 expressions as well as evaluating their roles in the tumorigenesis and the biological behavior of Ameloblastoma and Ameloblastic Carcinoma.Methods: Tissue samples are composed of 34 archived histopathologically confirmed cases of (19 Conventional Ameloblastomas, and 15 Ameloblatic Carcinomas). Sections were subjected to Immunohistochemical staining according to a standard protocol by applying antibodies to SOX2, and GPC3.Results: SOX2 and GPC3 expressions in recurrent Ameloblastoma were significantly higher than non- recurrent cases. Ameloblastic Carcinoma showed the highest immune-reactivity to SOX2 and GPC3 compared to the Conventional Ameloblastoma. Desmoplastic Ameloblastoma showed the highest scores of SOX2 and GPC3 compared to the other subtypes.Conclusions: SOX2 and GPC3 can be used as a panel for diagnosing the aggressive and the malignant odontogenic tumors accurately. Desmoplastic Ameloblastoma behaves more aggressively than other Conventional Ameloblastoma subtypes.