OBJECTIVEThe surgical anatomy of the infratemporal fossa and parapharyngeal space is often not properly understood by neurosurgeons, because these areas are more related to other medical disciplines. This article provides a detailed description of the infratemporal fossa and parapharyngeal space anatomy in cadaveric specimens and offers a neurosurgical perspective on a surgical approach that allows wide exposure and complete resection of giant tumors in this location.METHODSTen cadaveric specimens were prepared for anatomic study. Dissections were performed to emphasize the relationship between bone, muscles, and neurovascular structures and to simultaneously expose the middle cranial fossa, the infratemporal fossa, and the parapharyngeal space. Ten patients with giant lesions in these areas (with maximum tumor diameter >8 cm) were treated via this approach.RESULTSThe main obstacles to approaching the infratemporal fossa and the parapharyngeal space are the zygomatic arch, the parotid gland, the facial nerve, and the ascending ramus of the mandible. Thus, by combining a pterional-zygomatic craniotomy with transmandibular access, working up and down the parotid gland, the exposure is wider and safer. Among the 10 patients treated, tumors were totally resected in 7, subtotally resected in 2, and partially resected in 1. Morbidity was unremarkable, and, in 8 patients, clinical status improved dramatically.CONCLUSIONThe zygomatic-transmandibular approach allows resection of giant lesions in the middle cranial base, when they are invading the infratemporal fossa and parapharyngeal space, with a low morbidity rate.