The prognosis of metastatic melanoma is poor. Pre-targeted treatment era, the combination of interferon-alpha (IF-alpha) plus chemotherapy had been used and have generally short response duration. Herein, we present a metastatic melanoma case that achieved long-term durable complete response (CR) IF-alpha plus chemotherapy and IF-alpha maintenance therapy and had lower Regulatory T (Treg) cells. A fifty-year old woman was admitted to the hospital with metastatic melanoma. Lactate dehydrogenase (LDH) level was 660 U/L. The percentage of CD4+CD25+ Treg cells was 2.4% in CD4+ lymphocytes. The IF-alpha plus chemotherapy and IF-alpha maintenance were administered. After six courses of chemotherapy, CR was achieved. Vitiligo and hypothyroidism occurred. The patient has remained in CR for approximately 7 years until second pleural metastases were detected and death. The patient has positive prognostic factors such as induction of autoimmunity, small tumor volume, mild elevated LDH level, and lower Treg cell percentage. She survived long term with CR after IF-alpha treatment with concurrent chemotherapy and maintenance. IF-alpha plus chemotherapy may be a treatment option for metastatic melanoma in selected cases who cannot reach new targeted drugs. (C) 2015 Production and hosting by Elsevier B.V. on behalf of National Cancer Institute, Cairo University.