Giant-cell tumor rarely affects the sphenoid bone. Ten cases of this tumor seen at the Mayo Clinic are reviewed, bringing the number of cases in the world literature to 31. These tumors, which present in the second and third decades of life and are slightly more frequent in women than in men, may present with various symptoms, including headache, visual field defects, blindness, and diplopia. The symptom complex and roentgenographic findings are seldom, if ever, sufficiently characteristic to allow preoperative diagnosis. The microscopic differential diagnosis of giant-cell tumor of the sphenoid region includes giant-cell reparative granuloma, aneurysmal bone cyst, fibrous dysplasia, and "brown tumor" of hyperparathyroidism. Interesting features of this series include the presence of multifocal giant-cell tumor in one case, and the absence of Paget's disease of bone in every case. Complete follow-up review in these cases allowed a discussion of therapy and prognosis; it appears that subtotal excision with postoperative radiation therapy is the treatment of choice. While the histological appearance of giant-cell tumor is characteristic, caution must be exercised in interpreting small samples, and various reparative and metabolic disorders must be considered in the differential diagnosis.