We report a case of classical juvenile pityriasis rubra pilaris (CJPRP) in a 15-year-old boy with Down syndrome. The rash was extensive, severe, accompanied by intense itching and responded to low-dose etretinate. Xerosis and cheilitis were also present, suggesting that keratinization defects associated with Down syndrome may be involved in the pathogenesis of CJPRP. PRP is a rare dermatological disorder and to the best of our knowledge, this is the first reported case of CJPRP in a patient with Down syndrome.