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Background: Spontaneous remissions are rare but valid events in malignancies and in the past have led to the development of mainstay oncologic therapies. Case Report: We present a rare case of spontaneous regression of a solitary pulmonary melanoma metastasis with complete remission persisting for 28 months. Concurrent mediastinal nodal metastases progressed at the time of remission of the lung metastasis, but also demonstrated regression in follow-up fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) imaging. Metastatic nodes showed only minimal residual metabolic activity after 38 months of follow-up from the appearance of metastatic disease. Conclusion: This case report presents a rare spontaneous complete regression of a solitary pulmonary melanoma metastasis. Biological pathways involved in spontaneous regression in cancer are discussed.