Osteogenic sarcoma involving the sphenoid bone is an extremely rare condition. The rarity of the disease and the close proximity of the sphenoid bone to the various important intracranial structures poses a real challenge in diagnosis and surgical management of these lesions. An extended lateral craniofacial resection by a multidisciplinary approach was carried out in one such case to attempt en bloc resection. This case is presented and also a review of the relevant literature.