Historically, patients with locally advanced or metastatic melanoma have an extremely poor prognosis. In recent years, major breakthroughs in cutaneous melanoma treatment have led to remarkable improvements in patient outcomes. However, there are limited published data on the efficacy of these novel therapies in the treatment of mucosal melanoma due to rarity of the disease. We report a case of successful neoadjuvant targeted therapy with BRAF and MEK inhibitors followed by radical surgical excision in a patient with advanced malignant melanoma of the gallbladder.