Background: A common cause of admission for children with malignancy is neutropenic fever. When managed aggressively, adverse outcomes are rare, but many children are over treated with this approach. A risk stratification clinical decision rule (CDR), or serum markers of inflammation or infection, which predicted those at very low risk of significant complications could be used to reduce intensity and/or duration of treatment. Those at high risk could receive aggressive management. Objective: To identify, appraise and synthesise evidence on the discriminatory ability and predictive accuracy of CDR and serum markers of infection in febrile neutropenia (FNP) in children and young people undergoing treatment formalignant disease. Methods: The two reviews followed ‘‘Systematic reviews: CRD’s guidance for undertaking reviews in health care’’ and were registered with the HTA Registry of Systematic Reviews, CRD32009100453 and CRD32009100485. Study validity was assessed using a modified QUADAS questionnaire. Univariate random-effects models were used to synthesise test accuracy and narrative techniques to describe methodological aspects. Results: We found 20 studies describing 16 different CDR in 8388 episodes of FNP. No study compared different approaches and only one CDR was tested across multiple data sets. We found 26 studies examining 13 different serum markers in 3585 episodes of FNP. Inconsistency and heterogeneity limit the conclusions that can be drawn from these data. A range of methodological problems were identified. These included: small event-per-variable ratios, lack of shrinkage of prognostic estimates, failure to examine for non-linear relationships, use of data-driven variable selection and cutpoint determination techniques, premature categorisation of continuous data, lack of examination ofmissing data and no techniques to address this, and suboptimal examination of clustered data. Conclusions: 1. Firm clinical conclusions cannot be drawn through heterogeneity of CDR, tests and outcomes. 2. Risk stratification studies contain similar methodological problems as prognostic and diagnostic studies.