Many neoplasms of the head and neck extend centripetally, gaining access to the central nervous system via nerves through the skull base foramina. Often patients with perineural spread have been excluded from aggressive interventions given the overall poor prognosis and technical difficulty when addressing the perineural components. However, in carefully selected patients combined surgical approaches can provide the greatest potential for disease control as well as neural decompression for symptom relief. We performed a retrospective chart review of 20 consecutive patients who underwent skull base approaches for resection of tumors with intracranial extension via perineural spread from 2011 to 2014. Patients were evaluated for symptom change, surgical approaches, histopathology, adjuvant therapy, outcome, and prognosis. The most common presenting symptoms were pain or cranial nerve palsies. 55% of patients underwent endoscopic endonasal approaches, 50% transcranial approaches, and 15% underwent transfacial approaches. Overall 85% of patients reported symptom improvement in the post-operative period while 40% were completely asymptomatic following surgical resection. Ultimately, we observed a 45% mortality rate with an average survival of 8 months after diagnosis. In carefully selected patients, an aggressive multidisciplinary approach using a combination of surgical avenues to the skull base for the treatment of intracranial tumor via perineural extension can improve patient quality of life.