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Ameloblastoma is a common odontogenic epithelial tumor that exhibits various biological behaviors, ranging from simple cystic expansion to aggressive solid masses characterized by local invasiveness, a high risk of recurrence, and even malignant transformation. We report on two cases of unusually large solid ameloblastomas. We detected epithelial–mesenchymal transition-related gene expression and HRAS gene single nucleotide polymorphisms, providing possible molecular evidence of mesenchymal morphological changes in ameloblastoma. The detailed analysis of the pathogenesis of these two cases of ameloblastoma may deepen our understanding of this rare disease and offer promising targets for future targeted therapy.