The cranio-orbital foramen (COF) is located on the lateral wall of the orbit. It is a potential source of hemorrhage during deep lateral orbital dissection, since it functions as an anastomosis between the lacrimal artery and the middle meningeal artery. The aim of this study was to guide and facilitate the surgical procedures in the orbit, so as to determine a navigational area and the precise location of the COF and to standardize certain anatomical marks. The navigational area of the COF and topographical features were studied in 75 craniums with presented COF. 33 bilateral main COFs, 41 (18 on the right, 23 on the left) unilateral main COFs at the main cranium and 19 accessory COFs were studied for their navigational features on the orbit. The distances between the COF and the fronto-zygomatic suture, supraorbital notch, lateral angle of the superior orbital fissure (SOF) and Whitnall's tubercle were measured. The mean distance of the COF from the fronto-zygomatic suture, supraorbital notch, lateral angle of the SOF and Whitnall's tubercle was 26.3, 37.3, 92 and 27.1 mm, respectively. For the navigational area signs of the COF, areas of the orbit that form the transversal and vertical lines are generated on the reference points. Whilst the upper outer area of the orbit contains a potential bleeding risk, the bottom section of the outer column is identified as safe for the surgical operations of the lateral orbital wall. The fronto-zygomatic suture and Whitnall's tubercle are recommended as the most reliable navigational landmarks for identifying the COF. Hence, the transversal and vertical orientation of the COF should be mastered by the surgeons reconstructing the anterior base of the skull and the orbit.