Malignant melanoma is an aggressive skin cancer with no effective therapies currently approved for advanced disease. In the case presented, a 55-year-old female patient diagnosed with widespread disease from amelanotic desmoplastic melanoma was treated with 10 mg/kg ipilimumab as part of a phase II clinical trial (CA184-008). Prior to ipilimumab, three chemotherapeutic regimens had failed. Ipilimumab acts as a T-cell potentiator via blockade of cytotoxic T-lymphocyte antigen-4, a negative regulator of T-cell activation. Response to ipilimumab treatment was rapid, with a substantial drop in tumor volume within 12 weeks of treatment initiation. Based on the appearance of a new subcutaneous lesion, reinduction with ipilimumab was performed at Week 30. Following reinduction, the appearance of another small new lesion made the patient ineligible, as per protocol, for further dosing despite stabilization of her remaining lesions. Ipilimumab-associated immune-related adverse events were manageable with the use of treatment guidelines. It is of remarkable immunotherapeutic importance that no new lesions emerged and gradual tumor regression is still ongoing more than 2 years following the last dose of ipilimumab, despite daily administration of systemic corticosteroids to manage drug-induced AEs. The ongoing clinical response is maintained without any further antineoplastic treatment.