Display omitted Myeloproliferative neoplasms (MPN) are a group of clonal stem cell–derived hematopoietic malignancies driven by aberrant Janus kinase-signal transducer and activator of transcription proteins (JAK/STAT) signaling. Although these are genetically simple diseases, MPNs are phenotypically heterogeneous, reflecting underlying intratumoral heterogeneity driven by the interplay of genetic and nongenetic factors. Their evolution is determined by factors that enable certain cellular subsets to outcompete others. Therefore, techniques that resolve cellular heterogeneity at the single-cell level are ideally placed to provide new insights into MPN biology. With these insights comes the potential to uncover new approaches to predict the clinical course and treat these cancers, ultimately improving outcomes for patients. MPNs present a particularly tractable model of cancer evolution, because most patients present in an early disease phase and only a small proportion progress to aggressive disease. Therefore, it is not surprising that many groundbreaking technological advances in single-cell omics have been pioneered by their application in MPNs. In this review article, we explore how single-cell approaches have provided transformative insights into MPN disease biology, which are broadly applicable across human cancers, and discuss how these studies might be swiftly translated into clinical pathways and may eventually underpin precision medicine. Edited by Associate Editor Berthold Göttgens, this Review Series focuses on how the use of single-cell genomic and multiomic analyses are broadening our understanding of the complexity of leukemias and myeloid neoplasms. For acute myeloid leukemia, acute lymphoblastic leukemia, chronic lymphocytic leukemia, and myeloproliferative neoplasm, leading experts bring us up to date with recent data and speculate how these rapidly developing technologies may inform the directions of clinical care.