Antibodies to antigens in the Kell blood group system are usually immunoglobulin G, and, notoriously, anti-K, anti-k, and anti-Kpa can cause severe hemolytic transfusion reactions, as well as severe hemolytic disease of the fetus and newborn (HDFN). It has been shown that the titer of anti-K does not correlate with the severity of HDFN because, in addition to immune destruction of red blood cells (RBCs), anti-K causes suppression of erythropoiesis in the fetus, which can result in severe anemia. We report a case involving anti-Kpa in which one twin was anemic and the other was not. Standard hemagglutination and polymerase chain reaction (PCR)-based tests were used. At delivery, anti-Kpa was identified in serum from the mother and twin A, and in the eluate prepared from the baby’s RBCs. PCR-based assays showed twin A (boy) was