The purpose of this research is to compare serum cotinine cutoffs for nicotine/tobacco exposure and self-reported tobacco use in adolescents. National Health and Nutrition Survey, 2015-18, cotinine levels and tobacco questions were analyzed for frequencies; bivariate and logistic regression analyses. With serum cotinine as the gold standard, self-report of current smoking detected 40.5% who had tobacco/nicotine exposure cotinine levels (sensitivity = 40.5%). Self-report of current smoking and/or e-cigarette use detected 60.0% who had tobacco/nicotine exposure cotinine levels (sensitivity = 60.0%). In this nationally representative study, caution should be considered in relying upon adolescent self-reported cigarette use, and self-reported cigarette and/or e-cigarette use.