Purpose of review Myelodysplastic syndromes (MDS) have remarkably diverse somatic mutation patterns that can be challenging to interpret clinically. Yet, genetic information is increasingly available to physicians. This review will examine several implications of genetic diversity in MDS. Recent findings Somatic mutations can serve as clinically relevant biomarkers in MDS. Molecular subtypes may exist that share clinical features including risk of progression to acute myeloid leukemia, response to treatment, and overall survival. Several mutated genes are known to have prognostic value that is independent of common risk stratification tools. Mutations of several genes identify low-blast percentage patients with greater than predicted disease risk while only SF3B1 mutations predict lower disease risk than expected. Mutations of TP53 are associated with adverse features, yet demonstrate inferior outcomes than predicted by these risk factors. SF3B1 and TP53 mutations may identify clinically relevant subtypes of MDS and allow for better refinement of risk within these groups. Using somatic mutations to diagnose MDS is more challenging because they can occur in healthy individuals. Yet, patients with unexplained cytopenias have a high rate of clonal hematopoiesis that may be an important risk factor to identify clinically. Summary Patterns of somatic mutations are diverse in MDS, but can inform the prediction of prognosis and aid in its diagnosis.