The myelodysplastic syndromes (MDSs) are quite uncommon in children. Pediatric MDS is pathogenetically distinct from its adult counterpart and is characterized by a high frequency of germline mutations in GATA2, RUNX1, SAMD9, SAMD9L, and less frequently in genes encoding RAS signaling pathway components. The genomic landscape of pediatric MDS is distinct from that of adult cases and dominated by somatic driver mutations in SETBP1, RUNX1, ASXL1, and RAS pathway genes. A significant fraction of pediatric MDS cases develops in individuals with germline myeloid malignancy predisposition syndromes. These include the classic bone marrow failure syndromes (e.g., Fanconi anemia and Shwachman–Diamond syndrome), as well as several more recently described syndromes such as GATA2 deficiency or familial platelet disorder due to RUNX1 mutations. Three major types of pediatric MDSs are recognized in the International Consensus Classification, including refractory cytopenia of childhood, MDS with excess blasts, and MDS not otherwise specified. In this chapter, the molecular pathogenesis, histopathology, immunophenotypic findings of pediatric MDS are discussed in detail. Because several non-neoplastic disorders may pathologically mimic pediatric MDS, discussion of the differential diagnosis of MDS and the appropriate utilization of laboratory and molecular testing for accurate diagnosis is emphasized.