OBJECTIVE To evaluate the test performance of specific body mass index (BMI) percentile cutoffs for detecting children/adolescents with hypercholesterolemia. METHODS Cross-sectional analysis. METHODS National Health and Nutrition Examination Survey 1999-2004. METHODS Population-based sample of children (aged 3-18 years) with nonfasting total cholesterol (TC) and high-density lipoprotein (HDL) cholesterol levels and adolescents (aged 12-18 years) with fasting low-density lipoprotein (LDL) cholesterol and triglyceride (TG) levels. METHODS Individuals were classified as having hypercholesterolemia if they had a TC level greater than 200 mg/dL, HDL cholesterol level less than 35 mg/dL, LDL cholesterol level greater than 130 mg/dL, or TG level greater than 150 mg/dL, and sensitivity, specificity, and likelihood ratios were calculated for specific BMI percentiles. Receiver operating characteristic curves were constructed and area under the curve (AUC) was calculated. RESULTS Receiver operating characteristic curves using BMI percentiles to predict abnormal levels of TC and LDL cholesterol had AUC values (0.60 for TC level and 0.63 for LDL cholesterol level) that were less than the threshold of acceptable discrimination (between 0.7-0.8). Body mass index percentiles provided better discrimination for detecting children with abnormal HDL cholesterol and TG levels, with AUC values approaching levels of acceptable discrimination (0.69 and 0.72, respectively), although there are no specific guidelines regarding management of children with these abnormalities. CONCLUSIONS According to the American Academy of Pediatrics guidelines, abnormal levels of LDL cholesterol are used to determine which children require nutritional and pharmacologic therapy. Because BMI percentiles did not adequately identify children and adolescents with abnormal TC and LDL cholesterol levels, the new recommendations for targeted screening of obese children and adolescents may require further consideration.