Recommendations for screening children for high blood cholesterol remain controversial. The American Academy of Pediatrics, the American Heart Association, and the National Institutes of Health (NIH) Consensus Conference have recommended targeted screening of children with positive family history. We examined data from a sample of 108 Hispanic preschool children and their families to test targeted screening strategies. Thirty-seven children (34.3%) had total cholesterol levels of greater than or equal to 4.40 mmole/liter (170 mg/dl). Using the American Academy of Pediatrics definition of family history, sensitivity (proportion of those with high blood cholesterol with positive family history) was 0.57 (95% confidence interval, 0.40 to 0.73) and accuracy (overall proportion correctly classified) was 0.58 (0.48 to 0.68). Using the American Heart Association and NIH Consensus Conference definition of family history, sensitivity was 0.46 (0.30 to 0.63) and accuracy was 0.62 (0.52 to 0.71). Classification of children based on the mother's total cholesterol level of greater than or equal to 5.17 mmole/liter (200 mg/dl), the mother's low-density lipoprotein cholesterol level of greater than or equal to 4.14 mmole/liter (160 mg/dl), the mother's low-density lipoprotein cholesterol level of greater than or equal to 3.36 mmole/liter (130 mg/dl), or the child's own body mass index greater than or equal to 75th percentile was less sensitive and no more accurate. These findings indicate that current recommendations as well as other potential strategies for targeted cholesterol screening in young children have serious shortcomings and lend support to universal cholesterol screening in childhood.