miRNA-21 is among the most abundant and highly conserved microRNAs (miRNAs) recognized. It is expressed in essentially all cells where it performs vital regulatory roles in health and disease. It is also frequently claimed to be a biomarker of diseases such as cancer and heart disease in bodily-fluid based miRNA studies. Here we dissociate its contributions to cellular physiology and pathology from its potential as a biomarker. We show how it has been claimed as a specific predictive or prognostic biomarker by at least 29 diseases. Thus, it has no specificity to any one disease. As a result, it should not be considered a viable candidate to be a biomarker, despite its continued evaluation as such. This theme of multiple assignments of a miRNA as a biomarker is shared with other common, ubiquitous miRNAs and should be concerning for them as well.