Objective The aim was to investigate the influence of parents' negative mood state and parenting stress on behavior in children with newly diagnosed cancer. Methods A total of 123 parents (n = 58 fathers, n = 65 mothers) of 67 children with newly diagnosed cancer completed three questionnaires separately at the same time measuring parents' negative mood state, parenting stress, and child behavior problems. Results Parents' negative mood state was weakly correlated to more child behavior problems (r = 0.31, p < 0.01), and higher levels of parenting stress were strongly correlated to more child behavior problems (r = 0.61, p < 0.01). Mediation analyses indicated that the relationship between parents' negative mood state and child behavior problems (c = 0.29, p = 0.02 (fathers); c = 0.25, p = 0.04 (mothers)) became non-significant after mediating for parenting stress (c′ = 0.003, p = 0.98 (fathers); c′ = 0.10, p = 0.42 (mothers)). The indirect effect of parents' negative mood state and child behavior problems was only significant for fathers (95% CI [0.12; 0.51]), indicating that parenting stress mediates the effect between fathers' negative mood state and child behavior problems. Conclusions This is the first study to demonstrate the mediational role of parenting stress in fathers of a child with newly diagnosed cancer. Copyright © 2014 John Wiley & Sons, Ltd.