Depression and/or anxiety among adolescents aged 12-17 year are on the rise and increase the risk of negative outcomes that persist into adulthood. Current prevalence reports of depression in adolescents are based on dated analyses and do not include the often comorbid anxiety. The purpose of the study was to identify biological, psychological, and social factors that predict depression and/or anxiety in adolescents aged 12-17 years through a secondary analysis of data from the 2011-2012 National Survey of Children’s Health. The sample size for this study was 34,601 adolescents aged 12 – 17 of which, 2,405 had current depression and/or anxiety. One hundred four (104) of the total six hundred sixty-five (665) variables were identified for inclusion in the analysis through review of the literature and known clinical relevance. Variables were analyzed first through bivariate logistic regression to obtain c-statistics, followed by multiple logistic regression and classification and regression tree (CART) analysis. One subsample consisting of 60% of the original observations was used for modeling and generating the classification and regression tree; the other sample consisting of the other 40% of the original sample was used for validation purposes. Odds ratios were calculated based on the profile risk groups identified by the decision tree to quantify the odds of depression and/or anxiety in adolescents that met those specific profiles. The prevalence of depression and/or anxiety among adolescents with two or more chronic conditions, a behavioral problem, and whose mother’s mental health was rated as “poor” was 94% as compared to 7% in the general population. Additionally, the odds of depression and/or anxiety were 234.34 (95% CI: 225.78, 243.23, p < .0001) times the odds of depression and/or anxiety than those that did not have this profile. Implications for future work are discussed.