Cold agglutinin has specific importance in cardiac surgery field due to routine use of the systemic, topical hypothermia in cardiopulmonary bypass and cold cardioplegic solutions (4–12°C). We describe a case of coronary artery bypass in which cold agglutinin was detected intraoperatively; hence, cardiopulmonary bypass and myocardial protection strategies were changed. A simple and not expensive test is introduced to screen these patients before operation, as screening is not routine before cardiac surgery in many heart centers. In addition, we provide a literature review for surgical consideration and highlight some important concerns that need to be addressed.