Autism spectrum disorder characteristics have not been evaluated in Cornelia de Lange and Cri du Chat syndromes using robust assessments. The Autism Diagnostic Observation Schedule and Social Communication Questionnaire were administered to 34 participants with Cornelia de Lange syndrome and a comparison group of 23 participants with Cri du Chat syndrome (M ages 12.4 [SD = 3.8] and 10.3 years [SD = 3.6], respectively). Twenty-one participants with Cornelia de Lange syndrome (61.8%) scored above the autism cut-off on the Autism Diagnostic Observation Schedule compared to 9 with Cri du Chat syndrome (39.2%). Prevalence of autism spectrum disorder characteristics is heightened in Cornelia de Lange syndrome. The profile of characteristics is atypical to that of idiopathic autism.