: Autism spectrum disorder (ASD) may coexist with Down syndrome (DS). Most studies on this topic involve school-age children, adolescents, or adults with DS. This study looked at ASD symptoms, other mental health problems, and challenging behaviors in toddlers with DS at low risk of ASD. : We used screening tools for autism in toddlers; BISCUIT-Parts 1-3 and Q-CHAT. We compared four groups of children aged 17-37 months: DS, ASD, Atypical Development (AD), and Typically Developing (TD). : Children with DS showed lower symptoms of ASD than children with ASD (without DS) and higher than TD children, except for repetitive behaviors/restricted interests. For comorbid mental health problems and difficult behaviors, children with DS scored lower than children with ASD. There were no differences between children with DS and TD children in this regard. : The study results indicate that BISCUIT-Parts 1-3 are valid instruments to differentiate toddlers with DS from toddlers with ASD. However, they also show that toddlers with DS at low ASD risk are a very heterogeneous group when the ASD symptoms are considered. Autistic characteristics should be taken into account in supporting young children with this genetic condition.