Anatomic variations of the vital structures adjacent to the sphenoid sinus can be jeopardized during functional endoscopic sinus surgery (FESS). The knowledge of the size and extent of pneumatization of the sphenoid sinus (SS) is an important condition for adequate surgical treatment of its disease. The bony anatomic variations of SS as well as its relationship with adjacent vital structures were reviewed in this paper. The study was performed on 267 patients with a complaint of chronic or recurrent sinusitis. Computed tomographic (CT) scans were obtained upon completion of therapy. The evaluations of the sphenoid sinuses were regarded separately, so as 534 sides were examined. Especially bony anatomic variations as well as mucosal abnormalities of the sphenoid sinuses were examined. Pneumatization of the pterygoid process and anterior clinoid process were found in 39.7% and 17.2% of the patients respectively. Vidian canal protrusion was found in a total of 158 sides of which 60 were bilateral. These entities were encountered usually when pneumatization of the pterygoid process occurred. Carotid canal and optic canal protrusions were found in 5.2% and 4.1% of the patients respectively. Mucosal thickening, and polyps or cysts of sphenoid sinuses were detected in 20.6% and 4.5% of the patients respectively. There was a statistically significant correlation between pterygoid pneumatization and vidian canal protrusion (p<0.001), and vs. foramen rotundum protusion (p=0.004). While the optic canal protrusion was found significantly associated with the anterior clinoid pneumatization (P<0.001), there was no statistically significant correlation between a carotid canal protrusion and anterior clinoid pneumatization (p=0.250). Sphenoid sinus surgery is very risky, because of changing variations of the cavity. We are in the opinion that detailed data from CT scans of SS will enable the surgeon to interpret any anatomic variations and pathological conditions before initiation of the surgical therapy.