To examine whether childhood cancer survivors' perceptions of the impact of cancer are related to quality of life (QOL) and psychological distress. 621 survivors (aged 18-39 years) completed a mailed survey assessing distress and QOL. Hierarchical linear regression models analyzed the independent effects of perceived impacts of cancer on distress and QOL and the extent to which positive and negative perceptions attenuated the effects of covariates on outcomes. After accounting for perceptions of cancer's impact on their lives, employment/occupation status, marital/relationship status, and health problems were observed to be significant predictors of QOL and distress. Psychological distress and the mental health component of QOL appeared to be less influenced by sociodemographic status and health problems and more a function of how survivors perceive cancer as impacting their lives. Results suggest that distress and QOL are partially a function of survivors' perceptions of how cancer has affected them and continues to affect them in both positive and negative ways. Future research is needed to examine combinations of pharmacological, psychological and/or social interventions that are likely to result in better outcomes in this population. © 2011 Springer Science+Business Media B.V.