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The clinical and pathology findings in 2 sibs with xeroderma pigmentosum (XDP), complicated by metastatic malignant melanoma which underwent spontaneous regression, are described. The pathology of one of these patients showed features of possible spontaneous regression, namely foamy histiocytes, capillary proliferation, and a chronic inflammatory infiltrate which was devoid of malignant cells, suggesting the possibility that an immunological mechanism was at work. It was of interest that a recent review of 27 cases of spontaneous regression of metastatic melanoma since 1900 contained a patient with XDP. Adding our 2 cases, at least 10% of the spontaneous regressions of metastatic melanoma occurred in patients with XDP. This unusual association raised the question that the genotype for XDP may possibly foster control of metastatic malignant melanoma in some as yet unknown way.