Myelodysplastic syndrome (MDS) is a heterogeneous group of myeloid disorders. Allogeneic stem cell transplantation (alloSCT) is the therapeutic approach with a known curative potential for patients with MDS, which allows long-term disease control to be achieved. Despite advances in transplantation technology, there is still a considerable morbidity and mortality associated with this approach. Moreover, numerous controversies still exist regarding alloSCT in MDS. There is significant variability in the management of patients with MDS, especially of the intermediate-risk category and specifically in regards to the timing and use of transplantation. Modern genetic analysis has identified a variety of new mutations, which are associated with clinical phenotype and prognosis. Whether somatic mutations are important prognostic markers of response to alloSCT is little known. It is not clear whether somatic mutations can help to identify groups that are most likely to benefit from alloSCT. In this article, we review the current status of somatic mutations in MDS and focus on the prognostic impact of mutations in the context of alloSCT.