Autism spectrum disorder (ASD) includes disturbances in communication, imagination, and social interaction. In individuals with ASD, selective mutism is a common symptom of a communication disability. Selective serotonin reuptake inhibitors (SSRIs) have been recommended to treat selective mutism, especially after psychosocial interventions fail. However, the mechanism and efficacy of SSRIs in treating selective mutism remain unclear. Here we report the case of an adult male with ASD whose selective mutism was improved by aripiprazole but not SSRIs. To the best of our knowledge, this is the first such case report. We believe that our patient's case highlights the value of differentiating between psychopathology and psychopharmacology when examining ASD symptoms.