Heterophile antibodies are immunoglobulins produced by the immune system in response to exposure to animal and bacterial antigens, blood transfusions, autoimmune disorders, hematologic malignancies, dialysis, and pregnancy. Recently, these antibodies have garnered significant attention due to their impact on the accuracy of laboratory test results. Heterophile antibodies can bind not only to specific antigens but also to those from different species, including the antibodies used in laboratory tests. This cross-reactivity with foreign proteins is the basis for their interference in immunological assays, such as those measuring cardiospecific troponins (cTn). This manuscript reviews the literature on cases of heterophile antibody interference in troponin testing and proposes an algorithm for identifying such interference when clinical discrepancies arise. Recognizing and addressing heterophile antibody interference is crucial, particularly for tests like those for troponins, which are key biomarkers in the diagnosis and management of emergency and intensive care patients. The literature emphasizes the need for accurate procedures to distinguish true cardiac damage from false positives, thereby preventing unnecessary additional tests and hospitalizations.