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We describe the case of a 60-year-old woman with a delayed hemolytic transfusion reaction (DHTR). She had a history of an ulcerative colitis, blood transfusion because of rectal bleeding, and surgical removal of descendent and sigmoid colon. At admission, laboratory data showed Hb 6.3 g/dL, reticulocytes 120×109/L, serum total bilirubin 1.2 mg/dL (direct bilirubin: 0.2 mg/dL). Pretransfusion antibody screening procedures were positive. A monospecific autoanti-Jka and three alloantibodies (anti-c, -E, -K) were identified by immunohematologic studies. The patient received two units of crossmatch compatible concentrated red blood cells. Six days later biochemical serum values showed Hb 6.2 g/dL, LDH 975 I.U./L and total bilirubin 2.95 mg/dL (direct 0.35 mg/dL). Crossmatches with red cell suspension of transfused blood units and a post-transfusion serum were repeatedly positive. Laboratory tests showed the presence of anti-S alloantobody in the serum and eluate. Moreover, pre-transfusion serum of the patient was retrospectively retested: anti-S was not detected. These data suggested a DHTR. The present case is unusual and interesting because of the association of a rare autoanti-Jka, non responsible for anemia, and four alloantibodies of which anti-S involved in a DHTR.