The timely diagnosis of acute coronary syndrome (ACS), in particular myocardial infarction (MI), is still one of the most challenging issues in medicine. The introduction into routine laboratory practice of assays for measuring the cardiospecific troponins has dramatically revolutionized the diagnostic approach and the recent development of methods with improved analytical sensibility (i.e., highly sensitivity [HS] assays), has further contributed to improve the negative predictive value of troponin testing but, contextually, has substantially lowered the clinical specificity of these markers. In particular, clinical studies have demonstrated the existence of an exercise-related increase of HS-troponins, with measurable values detectable in up to 94% of athletes undergoing endurance sports. This measurable amount oftroponin in blood would mirror an increased membrane permeability and early troponin release rather than reflecting a clinically threatening myocardial injury. As such, the measurable amount of cardiac troponins as assessed with the novel HS assays requires major clinical focus (i.e., serial measurement of cardiac biomarkers, detailed clinical history-taking, integration with ECG and imaging findings) to prevent misdiagnosis of ACS and/or MI in otherwise healthy persons.