Odontogenic tumors are a heterogeneous group of lesions originating from tissues involved in odontogenesis. Mixed odontogenic tumors comprise a group of lesions characterized by the presence of ectodermal and mesenchymal odontogenic tissues with or without the formation of hard dental tissues. Aim: To determine and compare the expression of caveolin-1, MOC-31, connexin-43 (Cx-43), and Ki-67 in ameloblastic fibromas (AF), ameloblastic fibrodentinomas (AFD), ameloblastic fibro-odontomas (AFO), and odontomas (O). Methods: Immunohistochemical analysis for caveolin-1, MOC-31, Cx-43, and Ki-67 was performed on eight AF, one AFD, five AFO, and six O. RESULTS Variable protein expression was identified in the epithelium and mesenchyme of most AF, AFD, and AFO with lower expression observed in O. Immunohistochemical analysis revealed significant differences in protein expression between AF and O (P = 0.0085) and between AFO/AFD and O (P = 0.0250). When evaluating individual proteins, a significant difference in MOC-31 expression was observed between AF and O (P = 0.0310), while Cx-43 expression differed between AFO/AFD and O (P = 0.0022) and between AF and O (P = 0.0310). Additionally, protein expression decreased with increasing age (P ≤ 0.0100). Conclusion: This immunohistochemical study suggested that the similarity in protein expression between AFD, AFO, and AF compared with O may be due to the biological proximity among these lesions at the protein expression level. Further studies with larger sample sizes and complementary techniques are required to validate these findings.