Pediatric non-Hodgkin's lymphomas (NHLs) are a heterogeneous group of malignancies with distinct clinical, pathological, immunological and genetic characteristics. More than 90% of pediatric NHLs belong to one of three major histological subtypes: mature B-cell neoplasms, lymphoblastic lymphomas and anaplastic large-cell lymphomas. The recognition that different subtypes require different treatment regimens resulted in therapeutic strategies leading to over 80% of patients being cured. On the other hand, patients with resistant or relapsed disease have a poor prognosis. Prognostic biomarkers have not yet been identified for all pediatric NHLs and, although some are very important for diagnosis and prognosis, others may be of questionable value. Discovery of new biomarkers suitable for clinical application may aid the diagnosis and classification of lymphomas, which should, in turn, lead to better patient stratification. Consequent development of new treatment and follow-up approaches should lead to more efficient and less toxic treatment in children with NHL.