The term hemolysis designates the pathological process of breakdown of red blood cells in blood, which is typically accompanied by varying degrees of red tinge in serum or plasma once the whole blood specimen has been centrifuged. Hemolyzed specimens are a rather frequent occurrence in laboratory practice, and the rate of hemolysis is remarkably higher in specimens obtained in the Emergency Department (ED) as compared with other wards or outpatient phlebotomy services. Although hemolyzed specimens may reflect the presence of hemolytic anemia, in most cases they are due to preanalytical sources related to incorrect procedures or failure to follow procedures for collection, handling and storage of the samples; some of these are typical of the ED. Since hemolyzed specimens are often an important cause of relationship, economic, organizational and clinical problems between the ED and the clinical laboratory, it is essential to develop effective processes for systematically identifying unsuitable specimens (e.g. by using the hemolysis index), differentiating in vitro from in vivo hemolysis, troubleshooting the potential causes, and maintaining good relations between the clinical laboratory and the ED.