Statement of the Problem: The sphenoid sinus is a common target of paranasal surgery. Functional endoscopic sinus surgery is likely to endanger the anatomic variations of vital structures adjacent to the sphenoid sinus.Purpose: The aim of this study was to determine the variations of sphenoid sinus and the related structures by using cone-beam computed tomography (CBCT).Materials and Method: In this descriptive-analytic study, CBCT images of 103 patients aged above 20-years were selected (206 sides). Degree of pneumatization of sphenoid sinus, pneumatization of the anterior clinoid process, pterygoid process, protrusion of optic canal, vidian canal, and foramen rotundum, as well as prevalence of sinus septa were recorded. Examinations were performed using On-Demand software (Version 1); data were analyzed by using chi-square test.Results: There was a statistically significant correlation between the pterygoid pneumatization and vidian canal protrusion (p< 0.001), and foramen rotundum protrusion (p< 0.001). The optic canal protrusion was found to be significantly associated with the anterior clinoid pneumatization and pterygoid process (p< 0.001). Statistically significant relationship was also observed between the carotid canal protrusion and pterygoid process pneumatization (p< 0.001).Conclusion: The anatomical variations of the sphenoid sinus tend to give rise to a complexity of symptoms and potentially serious complications. This variability necessitates a comprehensive understanding of the regional sphenoid sinus anatomy by a detailed CBCT sinus examination.Key Words: Sphenoid Sinus; Internal Carotid Artery; Optic Nerve;Pneumatization; Cone Beam Computed Tomography