The incidence of cutaneous melanoma in Europe is constantly rising, and there is no cure for the disease once metastases occur. Since melanoma expresses antigens which can be specifically recognised by the immune system, extensive investigations are undertaken to find a working anti-melanoma immune therapy. To date, none of the developed vaccines works in patients. We investigate the interactions between melanoma and the immune system, focusing on a role of intratumoral dendritic cells and immunosuppressive microenvironment, and present a hypothesis explaining why the vaccines are successful in vitro, but ultimately fail in clinical trails. We suggest, that in order to achieve a successful anti-melanoma immune therapy, local immunesuppression must be overcome.