Current prognostic models for myelodysplastic syndromes (MDS) do not allow the identification of patients with lower risk disease and poor prognosis that may benefit from early therapeutic intervention. We evaluated the characteristics of 856 patients with low or intermediate-1 disease by the International Prognostic Scoring System. Mean follow-up was 19.6 months (range 1-262). Of these patients, 87 (10%) transformed to acute myelogenous leukemia, and 429 (50%) had died. By multivariate analysis, characteristics associated with worse survival (P<0.01) were low platelets, anemia, older age, higher percent of marrow blasts and poor-risk cytogenetics. Although not included in the model, higher ferritin (P=0.007) and beta2-microglobulin (P<0.001) levels were associated with worse prognosis. This allowed the development of a scoring system in which patients could be grouped in three categories: category 1 (n=182, 21%) with a median survival of 80.3 months (95% CI 68-NA); category 2 (n=408, 48%) with a median survival of 26.6 months (95% CI 22-32) and category 3 (n=265, 31%) with a median survival of 14.2 months (95% CI 13-18). In summary, this analysis indicates that it is possible to identify patients with lower risk MDS and poor prognosis who may benefit from early intervention.