Autism spectrum disorder is a clinical diagnosis that is typically made by a physician based on reported and directly observed behavior in the affected individual. According to the updated diagnostic criteria in the DSM-5-TR, in order to receive a diagnosis of autism spectrum disorder, one must present with “persistent deficits in social communication and social interaction” and “restricted, repetitive patterns of behavior, interests, or activities.” These behaviors must begin in early childhood and affect one's ability to perform everyday tasks. Furthermore, the symptoms must not be fully explainable by intellectual developmental disorder or global developmental delay.

There are several factors that make autism spectrum disorder difficult to diagnose. First off, there are no standardized imaging, molecular or genetic tests that can be used to diagnose ASD. Additionally, there is a lot of variety in how ASD affects individuals. The behavioral manifestations of ASD depend on one's developmental stage, age of presentation, current support, and individual variability. Lastly, there are multiple conditions that may present similarly to autism spectrum disorder, including intellectual disability, hearing impairment, a specific language impairment such as Landau–Kleffner syndrome. ADHD, anxiety disorder, and psychotic disorders. Furthermore, the presence of autism can make it harder to diagnose coexisting psychiatric disorders such as depression.