Abstract Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-associated fatalities. The diagnosis of TRALI is challenging due to lack of pathognomonic laboratory tests and the diagnosis is mainly based on clinical and radiographic findings. The criteria for the diagnosis of TRALI include (1) onset: within 6 hours of transfusion; (2) oxygenation: PAO2/FiO2 ≤300 mm Hg regardless of positive end-expiratory pressure level or oxygen saturation of ≤90% on room air; (3) chest x-ray: bilateral infiltrates on frontal chest radiography; and (4) blood pressure: pulmonary artery occlusion pressure ≤18 mm Hg when measured or no evidence of left atrial hypertension. Although the pathogenesis of TRALI is not fully understood, two different hypothetical pathways have been postulated. One of the pathways is an antibody-mediated, one-hit event (immune TRALI, 89% of cases) and mainly related to the antibodies against the human leukocyte antigen (HLA) or human neutrophil antigen (HNA). The other pathway (nonimmune TRALI) is a two-hit event, and the risk depends on certain predisposing factors, such as underlying pulmonary diseases. However, diagnosis of mild TRALI is challenging due to absence of stridor, wheezing, and rales on physical examination and lack of typical chest x-ray features of TRALI. On the other hand, identification of mild TRALI is important in order to initiate appropriate donor investigation and limit the potential for more severe occurrence in other patients. Recently, we diagnosed a rare case of mild TRALI and report it as follows: A 47-year-old African American male was admitted for relapsed acute myeloid leukemia (AML) who developed therapy-related thrombocytopenia requiring platelet transfusion. Within 15 minutes of starting the transfusion, the patient developed acute dyspnea, hypertension, tachycardia, and hypoxemia with PaO2/FiO2 of 78.9 mm Hg and SaO2 of 92.4%. However, the chest x-ray showed no infiltrates. He was treated with IV steroids, antihistamines, and 15 L of oxygen by face mask with improvement of signs and symptoms within 90 minutes of the reaction. The diagnosis of mild TRALI was confirmed by the detection of anti-HLA class I antibodies in the donor’s plasma. We reviewed the literature, and only four cases of mild TRALI were reported. Mild TRALI can be caused by transfusion of fresh-frozen plasma (2/4), RBCs (1/4), and platelets (1/4). The initial symptoms usually include fever (3/4), chills (4/4), dyspnea (4/4), tachycardia (3/4), and blood pressure changes (2/4 increased in both systolic and diastolic BP, 1/4 increased in systolic BP, 1/4 increased in systolic but decreased in diastolic BP, and 1/4 decreased in diastolic BP). On physical examination, no stridor, wheeze, rales, or urticaria were found (4/4). Laboratory test showed a decrease in the WBC (4/4). Chest x-ray did not show obvious bilateral infiltration and therefore was not required. The symptoms improved rapidly in a few minutes (2/4) to several hours (1/4 in 2 hours and 1/4 in 4 hours). HLA testing showed HLA class I (4/4) or class II (2/4) antibodies in the donor’s plasma. In conclusion, identification of mild TRALI is critical but challenging because diagnosis is based principally on the clinical symptoms and there is no specific laboratory test for mild TRALI. We need to have a high index of suspicion for TRALI in any patient who experiences respiratory symptoms related to transfusion in our daily practice.