Cardiac troponin is extensively used as a biomarker in modern medicine due to its diagnostic capability for myocardial injury, as well as its predictive and prognostic value for cardiac diseases. However, heterophile antibodies, antitroponin antibodies, and macrotroponin complexes can be observed both in seemingly healthy individuals and patients with cardiac diseases, potentially leading to false positive or disproportionate elevation of cTn (cardiac troponin) assay results and introducing discrepancies in clinical interpretations with impact on medical management. In this review article, we describe the possible mechanisms of cTn release and the sources of variations in the assessment of circulating cTn levels. We also explore the pathophysiological mechanisms underlying antitroponin antibody development and discuss the influence exerted by macrotroponin complexes on the results of immunoassays. Additionally, we explore approaches to detect these complexes by presenting various clinical scenarios encountered in routine clinical practice. Finally, unsolved questions about the development, prevalence, and clinical significance of cardiac autoantibodies are discussed.