Multiple informants commonly disagree when reporting child and family behavior. In many studies of informant discrepancies, researchers take the difference between two informants’ reports and seek to examine the link between this difference score and external constructs (e.g., child maladjustment). In this paper, we review two reasons why difference scores cannot serve as unambiguous predictors of outcomes. Further, we use polynomial regression analyses to both test the validity of difference scores and provide a more direct test of the hypothesis that discrepancies in parent and child reports predict child psychopathology. Data from 218 parent-adolescent dyads (M adolescent age = 11.5 years, 51 % female; 49 % European American, 47 % African American) were used to predict adolescent-reported antisocial behavior and depression from parent and adolescent reports of parent-adolescent conflict, parental knowledge, parental acceptance, adolescent rule-breaking behavior, and adolescent pubertal development. Results demonstrate that analyses using difference scores do not provide valid tests of the utility of informant discrepancies in predicting adolescent psychosocial maladjustment. However, interaction terms in polynomial regression analyses provide evidence that informant discrepancies predict child psychopathology. Parent-adolescent informant discrepancies predict adolescent psychopathology but researchers should avoid using difference scores to measure informant discrepancies. Polynomial regression analyses provide more comprehensive and accurate tests of whether informant discrepancies predict child and adolescent psychopathology.