The diagnosis of acute myocardial injury requires a rise and/or fall of cardiac troponin (cTn) on serial testing, with at least one concentration above the 99th percentile value of a normal reference population according to the recently published Fourth Universal Definition of Myocardial Infarction.1 However, the magnitude of change in cTn that constitutes a significant rise and/or fall was again not specified in detail. High-sensitivity cardiac troponin (hs-cTn) assays can measure ten-fold lower concentrations of cTn with more precision than older assays, and can accurately quantify cTn in more than 50% of healthy individuals with a coefficient of variation of less than 10% at the 99th percentile. These hs-cTn assays are also able to detect the normal variations in cTn results that are due to biological variability. Understanding and quantifying the normal variations in cTn is important as this would allow significant changes to be better defined. Numerous studies have sought to investigate the biological variability of cTn over the last ten years. Such studies are usually conducted in healthy individuals, however individuals with chronic cardiac disease or chronic renal failure have also been examined. These studies have yielded varying results in regards to significant change values for cTn. In light of the recent redefinition for myocardial infarction, the purpose of this mini-review is to revisit the biological variability of cTn. In particular, we outline concepts for determining a significant change value, review the results of previous studies on the biological variation of cTn and discuss potential considerations for clinical practice.