Background: Ep-CAM, a transmembrane glycoprotein expressed in most epithelium in normal conditions, has diverse roles in these tissues, including in cell adhesion, proliferation, differentiation, cell cycle regu-lation, migration and intracellular signaling. It is also over-expressed in most malignant neoplasia, partic-ipating in the initiation, progression, and metastatic dissemination of the tumor. The expression and roles of this protein in oral neoplasia, particularly in odontogenic tumors, remain unestablished. The objective of this study consisted in analyzing the expression of this protein in ameloblastoma and tooth germ. Material and Methods: Ep-CAM (MOC-31) expression was evaluated by immunohistochemistry in tooth germs (TG) (n = 16) ameloblastomas (AM) (n = 60) and 2 ameloblastic carcinomas. Sections were visualized in their totality with an optical microscope, and positivity observed in cell membrane and cytoplasm was graded according to the following semi-quantitative scale: Neg, "essentially unstained", for negative sections or staining <5% of cells; + for staining of 5-50% of cells; ++ for staining >50% of cells. Results: Most tooth germs expressed MOC-31 (81.3%), strong staining was observed both in the inner epithelium of the enamel organ and in the adjacent stellate reticulum. 16.7% of the AM cases showed MOC-31 expression, the immunoexpression expression was diffuse at the cytoplasmic and membrane level. The only two cases of ameloblastic carcinoma included were strong positive to MOC-31. No correlation was observed between protein expression and gender, age, clinical variants, or histological subtypes. Conclusions: Overexpression was found in TG and ameloblastic carcinoma compared to AM; further studies with different experimental strategies are suggested to clarify the biological significance of this finding.