Background: Maspin is a member of serine protease inhibitor (serpin) superfamily that is considered as an epithelial-specific tumor suppressor. CD34 is transmembrane glycoprotein that could be used as a sensitive vascular marker and useful predictor of tumor progression. Aim of study: To investigate the expression of maspin and CD34 in normal oral mucosa, different types of ameloblastoma and ameloblastic carcinoma. Materials and Methods: A total of 25 cases were used in this study and the achieved samples were divided into the following groups; normal gingival mucosa (n =5), unicystic ameloblastoma (n = 5), multicystic ameloblastoma; plexiform and follicular variants (n = 10 divided into 5 for each variant) and ameloblastic carcinoma (n = 5). To confirm the diagnosis and inclusion of the samples in the study, first 5-micron sections were prepared and were stained using hematoxylin-eosin staining protocol. Then, the blocks were prepared for immunohistochemical staining for maspin and CD34. Statistical analysis was used to compare maspin and CD34 among groups. Results: Immunohistochemical study revealed positive maspin expression in all groups however significant decrease in its expression and tumor progress was detected with the least expression in ameloblastic carcinoma. On the other hand, the vascular endothelial cells within lamina propria were positively stained with CD34 in all groups. Unexpectedly, there was concomitant significant decrease in CD34 expression and tumor progress with the least expression in ameloblastic carcinoma. Conclusion: Maspin is normally expressed in oral mucosa and further researches are recommended to clarify its role in normal adult odontogenic tissue. Moreover, maspin expression could be used as an accurate determining factor in prognosis and prediction of the odontogenic tumor progress and having superior exactitude in comparison with the angiogenic marker CD34.