Odontogenic keratocysts and central giant cell granulomas are distinct entities of separate origin that may appear simultaneously in the jaw, making them difficult to differentiate. The objectives of this paper are to report a case of a 54-year-old man presenting with a large lesion in the right mandible and to describe the histological characteristics of that lesion. Imaging revealed tumefaction and multilobulation. The case was surgically managed. Histopathological examination revealed that the lesion was a hybrid of an odontogenic keratocyst and a central giant cell granuloma. It remains unclear as to whether this lesion represented a coincidental or related injury. Since both types of lesion involved have a high rate of recurrence, however, long-term follow-up is scheduled.