EZH2 mutations are associated with a poor prognosis in myelodysplastic syndromes (MDS). In this video, recorded at the 2018 Society of Hematologic Oncology (SOHO) Annual Meeting in Houston, TX, Rashmi Kanagal-Shamanna, MD, of the MD Anderson Cancer Center, Houston, TX, discusses her work investigating the role of EZH2 mutations in MDS pathology. She highlights genetic and clinical correlates of EZH2 mutations, including an increased likelihood of multilineage dysplasia and chromosome 7 alterations, concluding that EZH2 has a tumor suppressor role in MDS.