Pediatric malignancies are uncommon and many have overlapping morphologic features, which together present diagnostic challenges. Cytopathology is recognized as an accurate and cost-effective modality for the diagnosis of pediatric malignancies in resource-limited countries, but is underused for this purpose in the United States. This review focuses on the cytopathology of pediatric malignancies with the goal of demystifying cytologic diagnoses of these entities. Differences between malignancies in young patients and adults are discussed, and key epidemiological features of childhood malignancies are highlighted. In addition, the use of cytopathology in different geographical settings is contrasted to illustrate the impact of variable usage on the incidence of malignancy and the types of tumors observed in cytologic specimens. A review of the pattern-based approach to differential diagnosis is also incorporated, including the cytomorphologic features and ancillary studies that help to distinguish between various malignancies within each pattern.