Myelodysplastic syndrome (MDS) consists of a heterogeneous group of acquired hematopoietic stem cell disorders, characterized by bone marrow failure and leukemic transformation. Since hematological manifestations and clinical outcomes vary widely among MDS patients, a considerable number of studies have tried to identify the prognostic parameters for the stratification of patients into different risk groups. Based on reported risk-based studies, the International Prognostic Scoring System (IPSS) was proposed as a reliable risk assessment method for primary MDS patients, and several validating studies have clarified its usefulness. Critical prognostic parameters of the IPSS consist of chromosome findings, the percentage of marrow blasts, and the number of peripheral blood cytopenias. Although other laboratory findings, including several molecular alterations, have been identified as convincing prognostic factors in MDS, these molecular configurations were not selected as prognostic parameters in the IPSS, because analysis for these alterations were not routinely available for the management of patients with MDS. Because recent advances in molecular genetics may make it available as a routine work-up of MDS in the future, we discuss potential improvement of the IPSS by the addition of molecular analysis to the system, with particular reference to the configuration of the TP53 gene.