: Label-free surface-enhanced Raman scattering (SERS) has recently gained attention in the field of liquid biopsy as a rapid and relatively inexpensive technique that could significantly ease clinical diagnosis and prognosis by investigating a biofluid sample with a laser. Indeed, SERS spectra provide information about a set of metabolites present in the analyzed biofluid thereby offering biochemical insight into specific health conditions. Ergothioneine plays a key role since it is one of the few metabolites in biofluids that are detectable by label-free SERS. In the past decade, many studies characterizing biofluids or other biological samples have unknowingly linked this amino acid with crucial metabolic processes, including inflammation, in a plethora of diseases. However, since the SERS spectrum of ergothioneine has been reported only recently, most past studies inadvertently assigned what are now recognized as the spectral features of this compound to other molecules. The purpose of the present review is to summarize and re-evaluate these studies in light of the recent SERS characterization of ergothioneine so as to better recognize the role of Ergothioneine in many clinical conditions.
