Hemolysis and jaundice related to Rh incompatibility in the neonatal period has decreased substantially due to the widespread use of anti-D gammaglobulin in recent years. Nevertheless, the rate of subgroup mismatch in the etiology of hemolytic diseases of the newborn has increased significantly. In this article an 8-day-old newborn infant with "c" subgroup incompatibility and presenting with severe anemia, in whom hemolysis could be controlled with intravenous immunoglobulin infusion and subgroup appropriate blood transfusion, has been presented. Scientific studies have demonstrated that the hemolytic disease of patients who don't have major blood group incompatibility but carry anti-C antibodies can be rather serious. Therefore, subgroup mismatch should always be kept in mind for newborns presenting with severe hemolytic anemia, and transfusion or if necessary exchange transfusion should be provided with subgroup matched blood products.