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Purpose: Treatment of tumors arising in the upper parapharyngeal space (PPS) or the floor of the middle cranial fossa is challenging. This study aims to present anatomical landmarks for a combined endoscopic transnasal and anterior transmaxillary approach to the upper PPS and the floor of the middle cranial fossa and to further evaluate their clinical application. Methods: Dissection of the upper PPS using a combined endoscopic endonasal transpterygoid and anterior transmaxillary approach was performed in six cadaveric heads. Surgical landmarks associated with the approach were defined. The defined approach was applied in patients with tumors involving the upper PPS. Results: The medial pterygoid muscle, tensor veli palatini muscle and levator veli palatini muscle were key landmarks of the approach into the upper PPS. The lateral pterygoid plate, foramen ovale and mandibular nerve were important anatomical landmarks for exposing the parapharyngeal segment of the internal carotid artery through a combined endoscopic transnasal and anterior transmaxillary approach. The combined approach provided a better view of the upper PPS and middle skull base, allowing for effective bimanual techniques and bleeding control. Application of the anterior transmaxillary approach also provided a better view of the inferior limits of the upper PPS and facilitated control of the internal carotid artery. Conclusions: Improving the knowledge of the endoscopic anatomy of the upper PPS allowed us to achieve an optimal approach to tumors arising in the upper PPS. The combined endoscopic transnasal and anterior transmaxillary approach is a minimally invasive alternative approach to the upper PPS. [ABSTRACT FROM AUTHOR]