Ameloblastoma is the most common aggressive benign odontogenic tumor of the jaws. Ameloblastoma is a benign epithelial odontogenic tumor that typically arises in the mandible or maxilla or, rarely, in the immediate adjacent soft tissues. A clinical, radiographic and histopathological report is presented of a case of acanthomatous ameloblastoma in relation to molar in the left mandible of a 30-year-old healthy male. The histopathological examination of the removed specimen revealed the histopathological pattern of an acanthomatous ameloblastoma. The radiographic appearance of the lesion showed the presence of multilocular radiolucencies, which were crossing the midline, which is rarely found in ameloblastoma. Due to its rarity and lack of data, we take this opportunity to present a world first case of acanthomatous ameloblastoma which was crossing the midline.