Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal bone marrow (BM) disorders characterized by the presence of dysplastic maturation of hematopoietic cells coupled with one or more peripheral cytopenias and a propensity to progress to acute myeloid leukemia. This chapter reviews the most frequently encountered abnormalities in MDs exploring their clinical and genetic features. The diagnosis of all hematological malignancies, including MDS, begins with the appropriate clinical evaluation combined with expert pathological and genetic analysis. The genes involved in MDS fall into four main classes, namely, genes encoding hematopoietic transcription factors, epigenetic regulators of gene transcription, RNA splicing factors, or proteins that regulate cytokine signaling pathways.The role of cytogenetic analysis in MDS remains a pivotal element for establishing the diagnosis, prognosis, and therapeutic decisions, including the initiation of specific treatments and the follow‐up of altered clinical behavior of the disease.