We aimed to better characterize exceptional cases of long survivors (LSs) among patients with stage IV melanoma. We performed a comprehensive regional investigation in the Champagne-Ardenne region, France. During the period 1994-2003, 316 patients died of melanoma whereas 10 patients diagnosed with distant metastases had a subsequent survival time > 4 years. These 10 LSs were characterized by a long delay (median: 58 months) prior to distant metastases and by frequent subsequent complete remissions (CRs). Eighteen episodes of CRs, lasting 3-139 months (mean: 26.4), were documented in 9 patients, for single or multiple tumors, for metastases of any site and with any treatment, even including spontaneous CRs. Four of 8 evaluable patients had clinical and/or biological features of auto-immunity. At 31 March 2007, 3 patients had died of melanoma and 1 of a chemo-induced leukaemia. The median survival time was 65 months (range: 52-139). These data suggest that long survival in stage IV melanoma might depend less on the site of metastases and specific therapies than on the patients themselves and their spontaneous antitumor control.