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Basal cell carcinoma (BCC) is the most commonly diagnosed cutaneous cancer globally. Chronic exposure to environmental triggers and genetic predisposition are risk factors that contribute to the incidence of BCC. While most cases of BCC are treated surgically with curettage or simple excision, treatment options for advanced BCC, including metastatic BCC and locally advanced BCC, are limited as some may be considered unresectable. Advancements in the role of hedgehog signaling in the pathogenesis of BCC have resulted in the development of hedgehog pathway inhibitors as the best treatment for BCC. Germline or somatic mutations in hedgehog pathway signaling components (Smoothened, Patched-1, etc.) result in constant activation of this pathway. Sonidegib and vismodegib are synthetic mimetics of hedgehog pathway inhibitors that are indicated for many subtypes of advanced BCC. We report an unusual case of locally advanced BCC in a 61-year-old male who suffered from a growing BCC for at least six years. After eight months of hedgehog pathway inhibitor (HHI) therapy, the patient reported dramatic improvements in his BCC and complete regression of smaller BCCs previously noted on his upper extremities. The patient reported only minor adverse events including hair thinning, weight loss, and rapidly growing nails., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Koch et al.)