In the Diego blood group, the frequency of the Di(a + b +) or Di(a + b -) phenotype among Chinese in Taiwan is estimated to be 3.2%. Here we report a case of severe hemolytic disease caused by anti-Di(a). The baby's total bilirubin elevated to 23 mg/dl at the age of 72 hours. A blood exchange transfusion and phototherapy were performed. We suggest to include Diego positive cell panels in testing antibody specificities that are likely to be encountered in this population.