Potentially resectable, advanced stage melanoma in the form of extensive palpable adenopathy or limited systemic metastases presents a significant challenge but also offers the prospect of long-term disease control. Although surgical resection is the mainstay of therapy, involvement of a multidisciplinary team is required for optimal management of these special situations. These patients need to be evaluated preoperatively by the team, discussed at a multidisciplinary conference, and treated by experienced physicians with access to the full spectrum of modern surgical and oncologic therapy. Surgical resection is generally extensive and may require en bloc resection of important anatomic structures. Adjuvant radiation or systemic therapy is required in many patients to help achieve durable regional and systemic control of disease. In addition, novel therapies, such as neoadjuvant chemotherapy, targeted therapies, or investigational intralesional therapies, may ultimately play a role in the management of these difficult clinical situations and require further evaluation, as preliminary studies show some encouraging results.