OBJECT A relative paucity of information exists regarding outcomes from craniofacial resection for advanced nonmelanoma skin cancers involving the skull base. In light of advances in surgical technique and adjuvant therapy protocols, the authors reviewed their surgical experience to determine disease control rates, overall survival (OS), morbidity, and mortality. METHODS A retrospective review of 24 patients with nonmelanoma cutaneous cancers with skull base involvement treated with craniofacial resection at The University of Texas MD Anderson Cancer Center from 1994 to 2012 was performed. Of these patients, 19 (79%) had squamous cell carcinoma (SCC), 4 (17%) had basosquamous carcinoma (BSCC), and 1 patient (4%) had adenocarcinoma. Factors as assessed were prior treatment, TNM staging, tumor involvement, extent of intracranial extension, margin status, postoperative complications, recurrence, disease status at last follow-up, and long-term survival. The majority of tumors were T4 (67%) according to the TNM classification; perineural extension was noted in 58%, cavernous sinus involvement in 25%, and dural involvement in 29%. RESULTS Postoperative complications occurred in 4 patients (17%) including 1 death. Kaplan-Meier estimates were calculated for OS and progression-free survival (PFS). Median OS was 43.2 months with an 82% 1-year OS and 37% 5-year OS; the median PFS was 91.2 months. Margin status was positively associated with median OS in SCC (91 months [for negative margins] vs 57 months, p = 0.8) and in BSCC (23.7 vs 3.2 months, p < 0.05). Postoperative radiotherapy was associated with improved median OS (43.2 vs 22 months, p = 0.6). Brain involvement was uniformly fatal after 1 year, while cavernous sinus involvement (31 vs 43 months, p = 0.82), perineural disease (31 vs 54 months, p = 0.30), and T4 stage (22 vs 91.2 months, p = 0.09) were associated with worsened OS. Similar associations were found with median PFS. CONCLUSIONS Aggressive multimodality management with surgery and postoperative radiotherapy can positively impact locoregional control and OS. With improvements in technique and adjuvant therapy protocols, treatment can still be considered in situations of perineural disease and cavernous sinus involvement and as a salvage option for patients in whom prior treatment has failed. As patients with advanced NMSCs often have few options, craniofacial resection, as part of a coordinated multimodal management plan, is justified if it can be performed safely.