OBJECTIVEOver the years, Meckel’s cave pathologies have been judged off-limits because of high rates of morbidity. Even though several studies have defined various surgical routes with tolerable morbidity and mortality rates, controversies related to the optimal avenue to treat different categories of Meckel’s cave and cavernous sinus neoplasms persist.With unceasing energy to cultivate minimally invasive neurosurgical approaches, the endoscopic endonasal route has been tested, and the approach effectively performed, to provide a valid surgical window to these areas. In this dynamic and challenging scenario, another ventral endoscopic minimally invasive route—that is, the superior eyelid endoscopic transorbital approach—has been very recently proposed, and used in selected cases, to access the cavernous sinus and Meckel’s cave regions.METHODSThe authors report the technical nuances of a combined and simultaneous endoscopic endonasal and transorbital surgical treatment of a patient with a Meckel’s cave schwannoma. The operation involved collaboration among neurosurgery, otorhinolaryngology, and ophthalmology (oculoplastic surgery). The patient recovered well, had no neurological deficits, and was discharged to home 3 days after surgery.RESULTSThe multiportal combined route was proposed for the following reasons. The endonasal approach, considered to be more familiar to our skull base team, could allow control of possible damage of the internal carotid artery. From the endonasal perspective, the most inferior and medial portion of the tumor could be properly managed. Finally, the transorbital route, by means of opening the lateral wall of the cavernous sinus via the meningoorbital band, could allow control of the superolateral part of the tumor and, most importantly, could permit removal of the portion entering the posterior cranial fossa via the trigeminal pore. Simultaneous surgery with two surgical teams working together was planned in order to reduce operative time, hospital stay, and patient stress and discomfort, and to ensure “one-shot” complete tumor removal, with minimal or no complications.CONCLUSIONSThis study represents the translation into the real surgical setting of recent anatomical contributions related to the novel endoscopic transorbital approach and its simultaneous integration with the endoscopic endonasal pathway. Accordingly, it may pave the way for future applications related to minimally invasive, multiportal endoscopic surgery for skull base tumors.