BACKGROUND: Children of patients with cancer are at increased risk for developing emotional and behavioral problems. This study explored the prevalence and predictors of emotional and behavioral problems in Children of cancer patients in a multisite research project. METHODS: A cross-sectional sample of N = 235 families was recruited simultaneously in 5 university medical centers. The participants, including parents (N = 402) and children (N = 324; ages 11-21 years) completed standardized questionnaires. Emotional and behavioral problems in children were measured by the Strengths and Difficulties Questionnaire (SDQ). On the basis of previous research and using a mixed-model approach, child-, parent-, family- and cancer-related variables were examined in addition to socioeconomic status as potential predictors. Descriptive statistics and a multiple random coefficient model were used in the analyses. RESULTS: Compared to norms, Children of cancer patients show increased mean levels of emotional and behavioral symptoms. The best predictor of emotional and behavioral problems from the perspectives of the child, the healthy parent, and the ill parent was general family dysfunction. Although family dysfunction was identified as the main predictor, the analysis revealed that the main part of variance was related to the individual child’s level. CONCLUSIONS: The results indicate that screening for child mental health problems and family dysfunction in oncological and psychosocial treatment units can identify the families most in need of psychosocial support. Psychological services need to be both family-oriented and child-centered and focus on family dysfunction to prevent mental health problems in children.