Isolated sphenoid sinus disease is an unusual entity that is encountered infrequently. With advances in antibiotic therapy and imaging techniques, the nature of isolated sphenoid sinus disease has significantly changed. More tumors and less inflammatory disorders are being encountered. We have retrospectively reviewed the medical records of patients who had undergone sublabial transseptal sphenoidotomy for isolated sphenoid sinus disease at Allegheny General Hospital for Pittsburgh between January 1985 and July 1989. Thirteen patients were identified with isolated sphenoid sinus disease who were successfully managed with sublabial transseptal sphenoidotomy. This approach allows maximal visualization and safety with minimal morbidity.