Destructive lesions of the clivus produce symptoms related to adjacent anatomic structures. Radiographic evaluation of a patient presenting with cranial neuropathies revealed a cystic lesion of the clivus, and surgical and histologic findings established a diagnosis consistent with a mucocele. There have been no previous reports in the literature describing a primary mucocele of the clivus. Appropriate treatment for these fluid-filled structures is marsupialization or exteriorization into the sphenoid sinus. A trans-septal sphenoidal approach was used in this case and is advocated as an effective means of managing cystic lesions in this area.