AnWj is a high-incidence antigen present on the red blood cells (RBCs) of greater than 99 percent of the general population. A 58-year-old man underwent autologous hematopoietic stem cell transplantation (HSCT) for stage IVa mantle cell lymphoma. This procedure was complicated by failure to engraft, necessitating ongoing support with blood components. After a 2-month period of uneventful transfusion support, the patient experienced increasingly severe reactions with fever and evidence of intravascular hemolysis, including hemoglobinuria. Testing revealed a complement-dependent anti-AnWj. Phenotyping confirmed the AnWja?? phenotype. Anti-AnWj was persistent despite immunosuppression, including treatment with allogeneic HSCT. Of interest, the pathogenesis of the downregulation of the graft AnWj in this patient is unclear.