<p>Simultaneous combined endonasal and transcranial surgery (SCENaTCS) is an accepted treatment option for giant pituitary tumors to prevent postoperative intratumoral hemorrhage from residual tumors. For various skull base pathologies, especially tumors invading multiple regions, SCENaTCS may be applicable, with advantages equal to or greater than those of staged surgeries using either the same or a different surgical approach. Twenty-six consecutive SCENaTCS procedures for 24 patients with highly complex skull base tumors were classified into following four types on anatomical basis: Type 1 (<i>n</i> = 8): giant pituitary tumors with a marked suprasellar component; Type 2 (<i>n</i> = 10): midline parasellar tumors extending laterally beyond the lateral limit of the internal carotid artery; Type 3 (<i>n</i> = 4): giant tumors arising from the infratemporal fossa and/or the pterygopalatine fossa, with extension toward both intracranial and paranasal spaces; and Type 4 (<i>n</i> = 4): large invasive clival tumors compressing the brainstem posteriorly. We analyzed the surgical results, postoperative complications, and outcomes with SCENaTCS to clarify the surgical advantages and technical pitfalls. The Karnofsky performance status score improved from preoperative state (mean: 79.6 ± 18.5) to 6 months after surgery (mean: 85.4 ± 12.5). Excluding patients who died of malignant transformation, the disease was controlled in most patients during a median follow-up period of 62.5 months. SCENaTCS is a safe and effective surgical option for the treatment of highly complicated skull base tumors. Intraoperative cooperation and communication between both surgeons and operating room set-ups that avoid interference between the surgeons are important to ensure comfortable surgical environments.</p>