Troponins measured by high-sensitivity methods (hs-cTn) are the current reference biomarkers to diagnose acute myocardial infarction. Conditions other than obstructive coronary heart disease may present an increase in hs-cTn. Heterophilic antibodies can interfere with the hs-cTn dosage. We report the case of a patient affected by rheumatoid arthritis, hospitalized for syncope and atypical chest pain. Serial blood samples documented high values of high-sensitivity troponin I and normal values of creatine kinase-MB and myoglobin. Echocardiogram, coronary angiography and electrophysiological study were normal. The use of heterophilic antibody blockers defined these values as false positive results. Therefore, to diagnose acute myocardial infarction, laboratory data should be integrated with clinical information and instrumental examinations. Marker release kinetics is crucial. Finally, there may be some possible causes of heterophilic antibodies (rheumatoid arthritis, Sjogren's syndrome, systemic lupus erythematosus, mixed cryoglobulinemia, hepatitis C, infections, cancer, sarcoidosis) that could interfere with biomarker dosage.