Transfusion management of patients alloimmunized against high-prevalence erythrocyte antigens is often problematic in emergency situations. In these patients, incompatible transfusion may be less harmful for the patient than delaying surgery, especially if the antibody is not clinically significant. We report an untransfused 75-year-old Caucasian man (blood group O) with an alloantibody against the Gerbich-2 (Ge2) antigen who required emergency cardiac surgery. Because cross-match compatible blood was not available in an acceptable timeframe, we performed a 'biological cross-match' with sequential transfusion of 20 and 50 mL and then the entire unit of incompatible red blood cells (RBCs) before surgery. When there were no clinical symptoms of adverse biological effects, we transfused two further incompatible packed RBCs during surgery. Subsequently, there was neither clinical nor laboratory evidence of major intra- or extravascular haemolysis, suggesting that this anti-Ge2 antibody was not clinically significant.