The study investigated whether the application of the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) diagnostic criteria for autism spectrum disorder results in different diagnostic outcomes compared with the DSM, fourth edition, text revision (DSM-IV-TR) in a cohort of Italian children with autism. To do so, both DSM-IV-TR and DSM-5 diagnostic criteria were applied to children believed to have autism. In comparison with the DSM-IV-TR criteria, DSM-5 criteria resulted in a lower proportion of children being diagnosed with autism. This difference in diagnostic outcome has implications about the access of children with autism to health care services as well as for their families being able to receive adequate support. We suggest that some DSM-5 diagnostic criteria for a diagnosis of autism should be revisited.