BackgroundThere is a lack of standardized definition for treatment-related mortality (TRM), which represents an important endpoint in cancer. Our objective was to describe TRM definitions used in studies of children, adolescents and young adults with lymphomas, solid tumors and brain tumors.MethodsWe conducted a systematic review of studies enrolling children, adolescents and young adults with lymphomas, solid tumors and brain tumors in which an anti-cancer intervention was randomized, or all study designs in which TRM was a primary or secondary outcome. We searched Ovid MEDLINE, EMBASE and Evidence-Based Medicine Reviews from 1980 to June 2013. Two reviewers evaluated study eligibility and abstracted data.ResultsIn total, 67 studies were included and consisted of 62 randomized therapeutic trials and 5 TRM studies. None of the studies (0/67) provided a definition for TRM. Only one randomized trial of rhabdomyosarcoma provided a definition of early death.ConclusionsWe were unable to identify any TRM definitions used in studies of children, adolescents and young adults with lymphomas, solid tumors and brain tumors. Given that a proportion of this patient population may receive intensive treatment, there is an urgent need for consensus-based definitions of TRM for use across clinical trials.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2407-14-612) contains supplementary material, which is available to authorized users.