The diagnosis of acute cardiac pathology is a clinical challenge in both the living and in the postmortem setting. Cardiac troponin (cTn) T and cardiac troponin I released from the contractile apparatus of cardiomyocytes into the circulation can be detected by sensitive and specific immunoassays and are the gold standard biochemical test for diagnosis of acute coronary syndromes (ACS). Recently with the advent of more sensitive detection methods, elevation in non-ACS has become apparent causing clinical confusion. In most cases, these elevations are related to subclinical cardiac damage and often confer poor prognosis in cTn-positive patients. Biomarkers of cardiomyocyte damage may be of value in routine hospital and medico-legal autopsy. A significant body of evidence has emerged since the late 1990s, assessing the clinical utility of cardiac troponin in biological fluids or in immunohistochemical staining of cardiac tissue to aid in the diagnosis of acute cardiac pathology when standard microscopic evidence is inconclusive. This chapter reviews the extensive literature on the subject and details the disparity between pericardial fluid and serum for the use of cTn in the postmortem setting.