Myelodysplastic neoplasms (MDS) are clonal disorders of hematopoietic cells characterized by peripheral cytopenias, morphologic dysplasia, ineffective hematopoiesis and risk of leukemic transformation (LT). Biology and clinical outcome within MDS are extremely heterogeneous, making individual risk prediction key for management and therapy decision. Prognostic scoring systems are used for risk prediction in MDS, and the current Revised-International Prognostic Scoring System (IPSS-R) is based on clinical variables and cytogenetic aberrations. Next generation sequencing (NGS) identified recurrently mutated genes, and molecular data have been used to refine the prognostication in MDS. However, there has been no commonly accepted standard for incorporation of NGS data into established prognostic scoring systems. The new Molecular International Prognostic Scoring System (IPSS-M) includes the mutation status of 31 genes in addition to cytogenetics, bone marrow blasts, hemoglobin level, and platelet count. In total, the IPSS-M requires 37 parameters including the TP53 multihit status (TP53^multi; combination of mutations, deletion or copy neutral loss of heterozygosity (CN-LOH)), KMT2A and FLT3 aberrations as well as a pattern of co-mutations for SF3B1. The IPSS-M provides a continuous patient-specific risk score grouped into six risk categories, defined as very low (VL), low (L), moderate low (ML), moderate high (MH), high (H) and very high (VH).