IMPORTANCE: Improvements in endoscopic technology and reconstructive techniques have made the endoscopic endonasal approach (EEA) a viable option to approach ventromedial lesions in the region of the hypoglossal canal. Prior to contemplating this surgical corridor, a thorough understanding of anatomic relationships and landmarks is essential to safely approach this region of the posterior skull base through an EEA. OBJECTIVE: To describe the surgical technique and anatomic landmarks in the EEA to the hypoglossal canal through referencing nasopharyngeal and posterior skull base anatomy. DESIGN, SETTING, AND PARTICIPANTS: Study of latex-injected cadaveric heads at the North Carolina Eye Bank Multidisciplinary Surgical Skills Laboratory at the University of North Carolina. INTERVENTIONS: An EEA to the hypoglossal canal was carried out bilaterally in 5 embalmed, latex-injected cadaver heads. MAIN OUTCOMES AND MEASURES: Cadaveric measurements of anatomic landmarks and relationships in the approach were obtained using a 10-cm surgical ruler and were reported as mean distances. Additionally, high-quality endoscopic images demonstrating the operative technique and anatomic relationships were obtained. RESULTS: The distance between the lacerum segment of the internal carotid arteries, the superolateral boundary, was 23.6mm(SD, 11.8 mm). The distance between the anterolateral edge of the occipital condyles, the inferolateral boundary, was 19mm(SD, 0.80 mm). The supracondylar groove was identified in the same anteroposterior plane as the nasopharyngeal orifice of the eustachian tube, and the anterior-most edge of the occipital condyle was 14mm(SD, 0.82 mm) from the posterosuperior edge of the salpingopharyngeal fold. Additionally, the transtubercular corridor was on the same plane as the superior edge of the torus tubarius in the anteroposterior axis. The distance to the hypoglossal canal from midline was 10 mm, which was found after completing drilling in the transcondylar and transtubercular corridors. Last, the hypoglossal nerve rootlets were identified entering the canal 6mminferiorly and 8mmlaterally from the vertebrobasilar junction. CONCLUSIONS AND RELEVANCE: The eustachian tube and other elements of nasopharyngeal anatomy are fixed landmarks that provide important points of reference when approaching the hypoglossal canal through an EEA. A thorough understanding of these anatomic relationships is vital in safely navigating this direct, surgical corridor to the posterior fossa.