Hybrid Odontogenic Tumors (HOT) are defined by the presence of two or more independent odontogenic tumors that originate from and affect the same maxillofacial site.

The present study is the first case report of a mandibular HOT consisting of Ameloblastoma, Calcifying Epithelial Odontogenic Tumor, and Ameloblastic Fibroma.

A 37-year-old otherwise healthy male presented with the chief complaint of swelling in the right mandibular body. On extraoral examination, mild facial asymmetry and stable occlusion were observed. Intraoral examination was significant for an erythematous, sessile, and indurated swelling in the buccal gingiva and mucosa, with ulceration in the lower right cervical pre-molar region. The computed tomography scan indicated a mandibular osteolytic, multilocular, and expansile lesion with areas of bone fenestration extending from the lower left lateral incisor to the right second molar. The patient underwent resection of the lesion through an intraoral approach with a 1 cm safety margin. Reconstruction was performed with a microvascularized fibula flap to restore function and achieve an acceptable cosmetic result. The patient is currently at a ten-year follow-up without recurrence.

Understanding the pathogenesis and pathophysiology of these complex lesions is necessary to improve comprehension, treatment, and surgical outcomes. Despite the rarity of hybrid lesions, they should be considered in the differential diagnosis, especially in large odontogenic pathologies. Due to microscopic variability, they require multiple biopsies and a thorough examination of the specimens to confirm the co-existence of two or more entities.