Basal cell carcinoma is the most common human malignancy, with an incidence exceeding all other cancers combined. Advanced basal cell cancer requires a multidisciplinary approach to management. The mainstay of treatment remains surgical excision with appropriate reconstruction. Some advanced tumors may require radical resections; however, extensive, high-risk surgery may be justified by the indolent biology of the disease and the likelihood of cure. Other options, such as radiation or systemic targeted therapy, may be considered in selected patients who either refuse or are not candidates for surgery. The focus of this article is primarily on management of these high-risk cases., Competing Interests: Disclosure M. Monroe has served on cutaneous squamous cell carcinoma advisory boards for Merck, Sanofi-Adventis, and Regeneron. He has research funding from the NIH (NIDCR), American Head and Neck Society, and Huntsman Cancer Institute. K. Kakarala has no disclosures., (Published by Elsevier Inc.)