A 51-year-old white man developed de novo a cutaneous malignant melanoma (Stage Ia) after a 30-month treatment period with TNF-alpha-antagonists, consecutively using infliximab, adalimumab and etanercept because of a recalcitrant moderate to severe plaque psoriasis. The patient previously had been treated fumarates for 4 years, cyclosporine A for 2 months and methotrexate for 5 weeks. He also received cycles of cream PUVA and UVB before and then between systemic medications. A possible causal connection between development of melanoma and immunosuppressive treatment is discussed in the light of recent literature. The termination of TNF-alpha-antagonist therapy following development of melanoma is recommended.