Marked differences have been found in molecular characteristics between pediatric and adult myelodysplastic syndrome (MDS) patients. The incidence of gene mutations associated with myeloid malignances in pediatric patients is lower than in adults, while the incidence of aberrant methylation is similar between them. It is also worth noting that novel molecular factors such as mitochondrial DNA mutations may play a role in the pathogenesis of childhood MDS. This article summarizes research advances in molecular biology of pediatric MDS.