In this report, we describe a case of pneumonia due to an infection with human coronaviruses (HCoVs)-OC43 in a pediatric leukemia patient with Down syndrome and febrile neutropenia. Not only the recently discovered HCoVs NL63 or HKU1 but also the prototype strains HCoV-OC43 and HCoV-229E have to be considered as respiratory pathogens in immunocompromised pediatric cancer patients. The routine utilization of polymerase chain reaction-based diagnostic tools would certainly elucidate the etiology of a relevant proportion of "pneumonias of unknown origin" in immunocompromised pediatric patients and would contribute to a better understanding of the role of HCoVs in this setting.