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Background/purpose: There are few studies comparing the expression of enamel proteins, such as amelogenin, and cytokeratins in cyst and odontogenic tumors like in ameloblastoma and odontogenic keratocyst, indicating that amelogenin could be a potential biomarker for the aggressiveness in the odontogenic tumors. The aim of this study was to evaluate if the expression of amelogenin, cytokeratin AE1/AE3 (CKAE1/AE3) and cytokeratin 14 (CK14) in cysts and odontogenic tumors with calcified matrices such as calcifying odontogenic cyst (COC), compound (CdO) and complex (CxO) odontomas, adenomatoid odontogenic tumor (AOT) and calcifying epithelial odontogenic tumor (CEOT) as an aggressiveness indicator. Materials and methods: Three COC, eight CxO, three CdO, twelve AOT, two CEOT and three dental germs were submitted to an immunohistochemistry panel of antibodies composed of amelogenin, CKAE1/AE3 and CK14. Results: CKAE1/AE3 and CK14 was present in all odontogenic epithelia. The amelogenin protein was detected in prismatic and amorphous calcified matrices of epithelial origin belonging to CxO, CdO, AOT, COC and the tooth germs used as controls. On the other hand, the CEOT was the only tumor or cyst studied that did not present immunostaining for amelogenin in calcified matrices. Conclusion: Amelogenin was detected in pathologies with a low or absent recurrence rate and excellent prognosis. CEOT was the lesion of greater clinical aggressiveness which did not express amelogenin. The presence of amelogenin in calcified matrices of odontogenic arise could be an indicator of low aggressiveness.