High-protein anti-D reagents prepared from pools of human serum have been used for routine RhD typing but, low-protein, saline reactive anti-D reagents formulated predominantly with monoclonal antibodies are in current use. Because some of the high-protein reagents contain macromolecular additives that may cause red cells coated with immunoglobulin to aggregate spontaneously, antisera with these additives may produce a false-positive reaction. A four-day old male was admitted due to severe jaundice. Initially, the RhD type of the newborn using a high-protein reagent was D-positive and then, using two low-protein reagents, it was D-negative. The blood type of the mother was B, CDe, and that of the newborn was B, CcdEe. The direct antiglobulin test on the newborn's RBC was positive. Anti-E and anti-c were identified in the mother's serum and anti-E only was identified in the newborn's serum. The newborn was treated with phototherapy for 10 days and discharged as recovered. We present a case of hemolytic disease of the D negative newborn, which showed a discrepancy between high protein anti-D and low protein anti-D. With a review of literature, the newborn was possibly misinterpreted as D positive.