Interferon alpha as adjuvant therapy in high risk melanoma delays relapses and distant metastasis as shown in large clinical trials and meta-analysis. There are clear signs that a long term low dose interferon therapy is especially effective in patients with micrometastasis (detected by sentinel node biopsy).Patient with stage IV melanoma (distant metastasis) need systemic therapy in most cases. Since until today there is no treatment that has been proven to prolong the overall survival for this patient population. We recommend according international guidelines that these patients are treated in the context of clinical trials in a melanoma reference center.