A risk-adapted treatment strategy is mandatory for myelodysplastic syndromes (MDS). We refined the WHO-classification based Prognostic Scoring System (WPSS) by determining the impact of the newer clinical and cytogenetic features and we compared its prognostic power to that of the revised International Prognostic Scoring System (IPSS-R). A population of 5326 untreated MDS was considered. We analyzed single WPSS parameters and confirmed that WHO classification and severe anemia provide important prognostic information in MDS. A strong correlation was found between the WPSS including the new cytogenetic risk stratification and WPSS adopting original criteria. We then compared WPSS vs. IPSS-R prognostic system. A highly significant correlation was found between the WPSS and IPSS-R risk classifications. Discrepancies did occur among lower-risk patients in whom the number of dysplastic hematopoietic lineages as assessed by morphology did not reflect the severity of peripheral blood cytopenias and/or increased marrow blast count. Moreover, severe anemia has higher prognostic weight in the WPSS vs. IPSS-R model. Overall both systems well represent the prognostic risk of MDS patients defined by WHO morphologic criteria. This study provides relevant information for the implementation of risk-adapted strategies in MDS.Leukemia accepted article preview online, 27 February 2015. doi:10.1038/leu.2015.55.