A patient with sphenoidal sinus carcinoma causing symptomatic panhypopituitarism is presented. The clinical and surgical anatomy of the sphenoidal sinus and the incidence and differential diagnosis of sphenoidal lesions are reviewed. Eighty-five cases of benign and malignant lesions were analyzed. It was found that orbital signs and symptoms are twice as likely to occur with malignant as with benign lesions. Lymphadenopathy, epistaxis, and involvement of the fifth, ninth, tenth, and eleventh cranial nerves were only found in patients with malignant tumors. Sinus films were often misleading. Sphenoidal tomography and sphenoidotomy were the only reliable diagnostic aids. An endocrinologic evaluation is needed prior to invasive procedures.