Background: Intraoperative hemolytic transfusion reactions (IHTR) are rare but potentially life-threatening events during surgery, necessitating prompt recognition and management to ensure patient safety. This case report illustrates the complexities of diagnosing and managing IHTR in a surgical setting. Case Report: A 36-year-old female with breast carcinoma undergoing a modified radical mastectomy developed an IHTR. Despite the absence of positive Coombs test results, the patient exhibited classic signs of IHTR including sudden onset of hemoglobinuria and respiratory distress post-transfusion. Immediate interventions included cessation of the transfusion and supportive care, followed by intensive monitoring and treatment in the surgical intensive care unit. Management and Outcome: The clinical team's rapid response to the adverse transfusion reaction involved re-intubation, intensive monitoring, and critical care management. These measures effectively stabilised the patient’s condition, highlighting the importance of preparedness and protocol-driven approaches in managing IHTR. Conclusion: This case underscores the challenges of diagnosing IHTR, particularly when standard diagnostic tests fail to confirm the condition. The successful outcome demonstrates the critical role of vigilance, rapid clinical judgment, and adherence to transfusion protocols in surgical settings.