Background and Objectives: The spinous foramen (FS) of the skull is an opening located in the greater wing of the sphenoid bone at the base of the skull, and it includes the middle meningeal vessels and the meningeal branch of the mandibular trigeminal nerve. The FS is commonly used as an anatomical landmark in neurosurgical procedures and neuroimaging of the middle cranial fossa because of its relationship with other cranial foramina and surrounding vascular and nervous structures. Thus, specific knowledge of its topography and possible anatomical variations is important regarding some surgical interventions and skull imaging. The aim of this study was to provide further details on the morphology of the FS of the skull by evaluating its topographic and morphometric relationships and correlating the findings with clinical practice. Materials and Methods: Thirty dried skulls of human skeletons from body donors from the collection of the Laboratory of Anatomical Microdissection at a medical school were used. The metric dimensions and variations of the FS and its relationship with adjacent bone structures were analyzed with an interface digital microscope. Results: The results showed the bilateral presence of the FS in all skulls; however, differences were observed in the shape, diameter, and topography in relation to the foramen ovale and the spine of the sphenoid. The FS was present in the greater wing of the sphenoid bone; however, in one skull, it was located in the lateral lamina of the pterygoid process. The FS was smaller than the foramen ovale. A round and oval FS shape was the most common (42.1% and 32.8% of the samples, respectively), followed by drop-shaped (12.5%) and irregular-shaped (12.5%) foramina. Conclusions: In conclusion, FS variations among individuals are common and must be considered by surgeons during skull base interventions in order to avoid accidents and postoperative complications.