The clinical heterogeneity of myelodysplastic syndromes (MDS) is best illustrated by the observation that these disorders range from indolent conditions with a near-normal life expectancy to forms approaching acute myeloid leukemia (AML). A risk-adapted treatment strategy is mandatory for conditions showing a highly variable clinical course, and definition of the individual risk has been based so far on the use of prognostic scoring systems. The authors have developed a prognostic model that accounts for the World Health Organization (WHO) categories, cytogenetics, transfusion dependency, and bone marrow fibrosis. This WHO classification-based Prognostic Scoring System (WPSS) is able to classify patients into five risk groups showing different survivals and probabilities of leukemic evolution. WPSS predicts survival and leukemia progression at any time during follow-up, and may therefore be used for implementing risk-adapted treatment strategies.