As an increase of diagnosis of Autism spectrum disorders (ASD) has been documented in the past 40 years, Down syndrome (DS), Fragile X syndrome (FXS) and tuberous sclerosis complex (TSC) each with co-morbid autism are three populations that are also increasingly prevalent. The purpose of this presentation is to provide clinicians with resources that review the characteristics of each disorder and how they present the same or differently with co-morbid autism. With all three possible co-morbid diagnoses, it is important to complete a comprehensive assessment in order to determine the appropriate diagnosis and how to best treat these individuals. Accordingly, this presentation discusses what is currently known about how to best assess and diagnose these individuals. Based on the conclusions drawn through reviews of the literature regarding individuals with DS-ASD, FXS-ASD and TS-ASD, differentiating characteristics that help determine a focus/emphasis of assessment have been determined.