Introduction: Minimal disease determination might serve for risk stratification, response evaluation and follow-up disease monitoring in childhood Non-Hodgkin lymphomas. Besides helping to judge minimal residual disease (MRD) during therapy, detection of minimal disseminated disease (MDD) at diagnosis may be of prognostic value itself. However, different subtypes, high cure rates, low patient numbers, limited initial tumour material and early progression pose challenges. Methods: Pubmed literature search on MDD and MRD in pediatric lymphomas. Results: Current clinical applications of minimal disease determination differ between the subtypes. For lymphoblastic lymphomas, both flow-cytometry detecting aberrant immunophenotypes and PCR-based assays for TCR- or Ig-rearrangements have been used for minimal disease measurement. A prognostic value of MDD could not be clearly established yet. MRD has not been analysed in larger patient cohorts so far. In Burkitt-lymphoma and -leukemia, MYC-Ig-fusion sequences or Ig-rearrangements enable minimal disease detection. While conflicting data on the role of MDD as risk factor for Burkitt lymphoma have been published, the prognostic value of early MRD in Burkitt leukaemia treated by risk-adapted chemotherapy has been described by two study groups. However, its role in the rituximab-era needs to be confirmed. In ALK-positive anaplastic large cell lymphoma (ALCL), MDD and MRD determined by qualitative or quantitative PCR for ALK-fusion transcripts are validated independent prognostic parameters. They are standard of care parameters assessed in routine clinically practice and used for patient stratification in clinical studies. Early MRD might even serve as endpoint for clinical trials and for guiding individual therapy. Conclusions and future outlook: Validation of MDD and MRD as prognostic parameters is required for all subtypes but ALCL. Next-generation sequencing based methods and the use of circulating cell-free tumour DNA as medium may provide new options and applications for minimal disease evaluation in childhood lymphomas. Keywords: diagnostic and prognostic biomarkers, minimal residual disease, non-Hodgkin (pediatric, adolescent, and young adult) No conflicts of interests pertinent to the abstract.