We report a case of concomitant skull base and atlanto-axial hyperpneumatization complicated by symptomatic pneumorrachis and cervical emphysema. A computed tomography (CT) scan of brain and spine highlighted a hyperpneumatization of the right temporal bone, the sphenoidal and occipital clivus, the occipital bone, and the first two cervical vertebrae, associated with epidural pneumorrrachis and cervical emphysema. A dehiscence in the right spheno-petrosal cleft as the site of abnormal communication between the hyperpneumatized cells and the epidural space was identified and repaired through an endoscopic transnasal transethmoidal approach. Postoperative course was uneventful and a 3-month postoperative CT scan of brain and spine showed a reduction of free air around the spinal cord, brainstem, and the cervical soft tissues and complete closure of the spheno-petrosal dehiscence. A comprehensive literature review focusing on pathogenesis, radiologic findings and treatment of cranio-cervical hyperpneumatization and its complications is herein presented.