Objective: The aim of this article is to study the role and advantages of combined microscopic/endoscopic procedures or exclusive endoscopic approaches in the treatment of petrous apex pathologies. Methods: The study was designed as a retrospective case series analysis. We included patients affected by pathologies of the petrous apex, who underwent microscopic/endoscopic-assisted or exclusive endoscopic procedures. Patient and pathology characteristics and surgical data (focusing on the involvement of the internal carotid artery (ICA) and facial nerve by the disease) were collected. Residual disease, detected through the endoscopic check, and the feasibility of endoscopic residual tumor removal were also evaluated. Finally, facial nerve and hearing functions were assessed pre- and postoperatively. Results: The records of 75 patients undergoing lateral skull base surgery for petrous apex lesions, from May 2009 to March 2019, were collected. In 17 out of 75 patients, an exclusive endoscopic procedure was possible. The remaining 58 patients underwent a combined microscopic/endoscopic approach. In 15 cases, residual disease was found and removed endoscopically at the end of the microscopic procedure; in eight cases, the residual disease was medial and/or inferior to the horizontal segment of the ICA, while in two cases, it was located in the fundus of the internal auditory canal. In five cases, it involved the labyrinthine segment of the facial nerve. Conclusion: Petrous apex surgery remains a traditional microscopic-based surgery, but the recent advent of endoscopic surgery has permitted an improvement in radicality minimizing the manipulation of neurovascular structures