The 22q11.2 deletion syndrome (22q11DS) is a genetic disorder associated with palatal abnormalities, cardiac defects, a characteristic facial appearance, learning difficulties, and delays in speech and language development. Various behavioral disorders and psychiatric illnesses have also been reported. There is much debate as to whether the behavioral problems are caused by factors such as medical discomfort, facial abnormalities or a lower intelligence, or whether they are independently related to the genetic abnormality (“behavioral phenotype”). We examined the relationship between intelligence level and behavioral problems. A group of 69 children with 22q11DS was compared with 69 children with craniofacial anomalies (CFA) using the child behavior checklist (CBCL). The matches between individual children were based on their total IQ scores. Use of the CBCL norm scores covered the corrections for age and sex. The group of 22q11DS children showed significantly more behavioral problems than the CFA group: this was especially apparent on the CBCL subscales “withdrawn,” “anxious/depressed,” “delinquent behavior,” “aggressive behavior,” “somatic complaints,” and “social problems.” We found no correlation between IQ score and behavioral problems in the 22q11DS group, which was remarkable because, comparable with the general population, intellectual disabilities were a predictor of behavioral problems in the CFA group. 22q11DS children with relatively higher IQs showed more problems of an internalizing than an externalizing nature, whereas the 22q11DS children with lower IQs showed various behavioral problems. The absence of a statistically significant correlation between intelligence and behavior problems in the group of 22q11DS children is tentative evidence for a 22q11DS behavioral phenotype. © 2007 Wiley-Liss, Inc.