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Abstract Introduction The use of endoscopic sinus surgery in the field of otorhinolaryngology is due to many reasons such as better visualization, the complex anatomy of the skull base and the relations between vital vascular and nervous elements, the crucial preoperative knowledge about the detailed anatomy of the area, and the computed tomography that is a useful tool for them to plan the safest route of surgery. The foramen rotundum (FR) is the inherent bony structure in the skull base located in the greater wing of the sphenoid bone on the floor of the middle cranial fossa, located adjacent to the nasopharynx, and often invaded by nasopharyngeal cancer and other malignant brain tumors. The This study aims to give a detailed description of anatomical variations of FR, as well as its relationships with the surrounding vital structures, to instruct a preoperative planning for endoscopic surgery. Methods The distances between the foramen rotundum and fixed anatomical landmarks like the nasal floor and pterygoid process were measured in 200 foramen rotunda of 100 patients older than 18 years old and without known skull base pathology. The patients included in this study were demonstrated and evaluated separately using a multislice computed tomography (CT) technique with DICOM viewing software (Osirix or Horos). Results The average horizontal distance between the FR and vidian canal (VC) on each side, vertical distance between FR and VC on each side, direct distance between the FR and VC on each side, FR diameter, rotundum angles, FRs and nasal floor angles, and FR and optic nerve distances calculated has no significant difference. The P values were 0.471, 0.521, 0.072, 0.283, 0.952, 0.661, and 0.663, respectively. The gender comparison in the present study showed no significant distances on both the right and left sides. The P values 0.765, 0.879, 0.621, 0.297, 0.992, and 0.227 were direct, horizontal, and direct distances, respectively. Conclusions This study provides more light on the anatomy of the foramen rotundum with the other anatomical/surgical key structures used in endonasal surgeries such as the lateral pterygoid plate and vidian canal.