The increased incidence of malignancies, especially acute leukemia, in Down syndrome has been clearly established. The association of Hodgkin's disease with Down syndrome has not been extensively documented, and only a few cases have been reported. We present here a case report of Hodgkin's disease in an 11-year-old female child with Down syndrome. The child presented with a stage IVB nodular sclerotic Hodgkin's disease and died of progressive disease. We also present a brief review of the mechanisms of development of malignancy in Down syndrome.