The etiology of childhood-onset aggression (COA) is poorly understood, but early COA can be considered as a strong risk factor for adult delinquency and criminal behavior. Callous-unemotional (CU) traits have been proposed as a developmental model of antisocial behavior. Catechol O-methyltransferase (COMT) has been associated with aggression, attention deficit/hyperactivity disorder (ADHD), and other psychiatric disorders. We report an association study between COMT single-nucleotide polymorphisms (SNPs), childhood aggression, and the CU trait in our sample of 144 children with scores at or exceeding the 90th percentile on the aggression subscale of the parent-reported Child Behavior Checklist and the Teacher's Report Form. The genotype analysis of rs6269 showed nominally significant association (P = .019) and rs4818 showed a trend (P = .064) with COA. Trends were observed for rs6269 and rs4818 with CU scores (P < .10) as well. The analyses stratified by ADHD, or gender showed no significant results. This is the first report to our knowledge evaluating COMT SNPs with the phenotype of high aggression in children with a possible role for the COMT marker in CU traits. Given the importance of CU traits in antisocial behavior, further investigation of COMT is warranted. Aggr. Behav. 39:45-51, 2013. © 2012 Wiley Periodicals, Inc.