High rates of psychiatric impairment in adults with 22q11DS suggest that behavioral trajectories of children with 22q11DS may provide critical etiologic insights. However past findings based on DSM disorders are extremely variable, moreover gender has not yet been examined. Dimensional CBCL ratings from 82 children, including 51 with the 22q11DS and 31 control siblings were analyzed. Strikingly consistent with rates of psychiatric impairment among affected adults, 25% percent of children with 22q11DS had high CBCL scores for Total Impairment, and 20% had high CBCL Internalizing Scale scores. Males accounted for 90% of high Internalizing scores and 67% of high Total Impairment scores. Attention and Social Problems were ubiquitous; more affected males than females (23% vs. 4%) scored high on Thought Problems. With regard to CBCL/DSM overlap, 20% of affected males as compared with 0 affected females had one or more high CBCL ratings in the absence of a DSM diagnosis. Behaviors of children with 22q11DS are characterized by marked gender differences when rated dimensionally, with significantly more males experiencing Internalizing and Thought Problems. Categorical diagnoses do not reflect behavioral gender differences in children with 22q11DS, and may miss significant behavior problems in 20% of affected males.