The recognition that genetic defects identify some pediatric solid tumors and may represent prognostic markers has provided cytologists with an extra tool for dealing with such tumors. Using some entities as archetypes, we discuss the importance of the association of fine needle biopsy and genetics, in the diagnosis, prognosis, and therapy selection of solid pediatric tumors. Immunocytochemistry is important to differentiate neuroblastoma, PNET/Ewing sarcoma, alveolar rhabdomyosarcoma, lymphoma, and desmoplastic small round cell tumor. Despite its usefulness in many cases, it is not conclusive and some of the aforementioned tumors even share the expression of some antibodies. The detection of specific diagnostic translocations will thus provide additional information and allows a precise cytologic diagnosis. Kidney tumors are also frequent in children. Although no genetic abnormalities have been identified so far in nephroblastoma, other kidney tumors, such as mesoblastic nephroma, whose cytology pattern can masquerade nephroblastoma, are also characterized by specific translocations. Kidney tumors in children have also been associated recently with typical genetic alterations such as Xp11.2RCC. Concerning prognosis and therapy selection, neuroblastoma is a sort of paradigm. The identification of MYCN oncogene status as an independent prognostic factor is determinant, not only in the assessment of clinical evolution, but also in the identification of risk groups, and consequently in the appropriate therapy selection. Cytopathologists should be aware of the genetic alterations characterizing pediatric tumors in order to collect extra material to perform cytogenetics, FISH, PCR, and Southern blotting, to achieve the correct identification of such genetic changes. Diagn. Cytopathol. 2008;36:678–684. © 2008 Wiley-Liss, Inc.