A two days-old newborn female patient with Down Syndrome was admitted to our hospital with complaint of vomiting. Physical examination was unremarkable except for the typical physical appearance of Down Syndrome. An abdominal radiography showed the double-bubble sign, characteristic for duodenal obstruction, and the patient was operated with prediagnosis of duodenal atresia. However, during the operation, Hirschsprung’s disease was suspected and the diagnosis was confirmed by rectal biopsy. In this study, we described the case of duodenal atresia together with Hirschsprung’s disease in a patient with Down Syndrome. Radiologists and pediatric surgeons should consider this issue for a correct diagnosis and treatment.