Children with autism spectrum disorder (ASD) show frequent maladaptive behaviors and difficulties in social communication and motricity. Various studies suggest that music-based interventions might help overcome these challenges. Yet, their findings are not conclusive, particularly regarding piano music. The current pilot study aims to present a new music-based intervention – the Piano Therapy program – and to explore its effects on social communication, motricity, self-care, and adaptive behavior skills in children with ASD. The program uses techniques derived from Applied Behavioral Analysis and active and receptive musical methods structured around a single instrument (i.e., piano). Sixty children with ASD were quasi-randomly assigned either to the Piano Therapy group or the control group. In the experimental group, the 4-month program was administered individually, twice a week. Using the Psychoeducational Profile - Third Edition (PEP-3) reports, the examiner and the caregivers assessed participants’ skills pre- and post-intervention. The findings indicate that the children enrolled in the Piano Therapy program show significant improvements in all the developmental areas assessed with PEP-3, compared to the control group. Although further research is required, these preliminary results have clinical implications for practitioners and bring new evidence about the beneficial effects of a piano-based intervention in individuals with ASD.