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Regression of metastatic melanoma is a rare event, and review of the literature reveals a total of 76 reported cases since 1866. The proposed mechanisms include immunologic, endocrine, inflammatory and metastatic tumour nutritional factors. We conclude from this review that although the precise mechanisms remain unknown, some event must trigger the immune system to produce a stronger than normal response that results in regression of the melanoma metastases. Immunologic studies of patients with regression may disclose the underlying mechanisms and lead to new therapies of disseminated melanoma.