Conceptually-driven investigations on the potentially modifiable predictors of individual differences among children with newly-diagnosed cancer may facilitate the identification of pediatric cancer patients at risk for maladjustment during the profound adversity associated with this life-threatening disease and aversive biomedical treatment. Within a risk and resistance theoretical framework, perceived stress and social support were investigated concurrently and prospectively within an exploratory design as predictors of negative affectivity (anxiety and depressive symptoms composite construct) in newly-diagnosed pediatric cancer patients at Time 1 (within one month after diagnosis), Time 2 (6 months postdiagnosis), and Time 3 (9 months postdiagnosis). Hierarchical multiple regression analysis findings indicate that perceived stress and social support have direct and independent effects on negative affectivity principally at the 9-month time interval. These findings are discussed in terms of the cognitive-behavioral treatment implications for enhancing child adjustment during the transition from the initial cancer diagnosis and aversive biomedical treatment to subsequent school and social reintegration.