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Object The midline skull base is an anatomical area that extends from the anterior limit of the cranial fossa down to the anterior border of the foramen magnum. Resection of lesions involving this area requires a variety of innovative skull base approaches. These include anterior, anterolateral, and posterolateral routes, performed either alone or in combination, and resection via these routes often requires extensive neurovascular manipulation. The goals in this study were to define the application of the endoscopic endonasal approach and to become more familiar with the views and skills associated with the technique by using cadaveric specimens. Methods To assess the feasibility of the endonasal route for the surgical management of lesions in the midline skull base, five fresh cadaver heads injected with colored latex were dissected using a modified endoscopic endonasal approach. Full access to the skull base and the cisternal space around it is possible with this route. From the crista galli to the spinomedullary junction, with incision of the dura mater, a complete visualization of the carotid and vertebrobasilar arterial systems and of all 12 of the cranial nerves is obtainable. Conclusions The major potential advantage of the endoscopic endonasal approach to the skull base is that it provides a direct anatomical route to the lesion without traversing any major neurovascular structures, obviating brain retraction. Many tumors grow in a medial-to-lateral direction, displacing structures laterally as they expand, creating natural corridors for their resection via an anteromedial approach. Potential disadvantages of this procedure include the relatively restricted working space and the danger of an inadequate dural repair with cerebrospinal fluid (CSF) leakage and potential for meningitis resulting. These approaches often require a large opening of the dura mater over the tuberculum sellae and posterior planum sphenoidale, or retroclival space. In addition, they typically involve large intraoperative CSF leaks, which necessitate precise and effective dural closure.