Detection of clinically significant alloantibodies during pretransfusion testing is essential before any blood transfusion. Sometimes, clinically insignificant antibodies unrelated to blood group antigen may interfere with routine testing. Their interpretation is often made only after tedious immunohematology workup resulting in the exclusion of all possible clinically significant antibodies. We encountered such incidence which interfered with crossmatching. In our case, direct antiglobulin test was negative, indirect antiglobulin test and autocontrol were positive with pan-reactive antibody screening test, and group-specific units were incompatible. After meticulous workup, we could find that these antibodies were directed against the enhancement media, low-ionic strength solution in this case.