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A man in his mid 60s with a history of resected primary cutaneous melanoma then developed metastatic BRAF V600E mutant disease involving lymph nodes, liver and bone. He was unable to tolerate 2 months in total of BRAF/MEK inhibitor therapy because of multiple toxicities and subsequently developed progression while off therapy. During this time, he underwent surgical aortic valve replacement for severe aortic stenosis with coronary artery bypass grafting. The latter procedure was complicated by an infection. Unexpectedly, post-operative restaging imaging demonstrated complete resolution without further anti-cancer therapy. The patient has remained in complete remission on surveillance alone for more than 6 years. Two years after surgery, he developed a new honeybee venom allergy, suggesting an alteration in immune responsiveness. This case highlights a rare and durable regression of metastatic melanoma temporally associated with major surgery and supports the hypothesis that surgery-associated systemic immune activation may contribute to long-term tumour control.