The method of randomized trials, as performed by the WHO Melanoma Program, has definitely been a legitimate clinical study design in patients with melanoma from about 1970 to the end of the last century. Three important results of these WHO trials have substantially influenced the approach of the clinician towards melanoma: (1) There is no role for elective regional lymph node dissection, (2) narrow local excision of the primary melanoma does not entail additional risks, and (3) adjuvant treatment with chemotherapy or immunotherapy after radical surgery for regional lymph node metastases has not, until now, shown any substantial benefit. A problem arises because randomized clinical studies require long periods of time for patients accrual and completion. Frequently their legitimacy is challenged due to the appearance of new parameters, both regarding staging (eg, the introduction of new technical method such as sentinel node biopsy) and prognosis. Therefore, it would be better to define different clinical study models to quickly test a hypothesis on a small group of selected patients in order to provide quick results. We believe that this is the future of clinical research in the new millennium, because it does not seem reasonable today to plan large clinical trials that need 10 years or more of accrual and follow-up without reaching definite conclusions.