Histopathological examination is one of the most important methods in diagnostics of connective tissue diseases. We encounter serious difficulties in its interpretation, especially in the early stage of changes. In this group of diseases, early and correct diagnosis is essential. Unfortunately, only with the progression of the disease new symptoms appear which enable definitive diagnosis. In consequence of diagnostic difficulties proper treatment is often implemented too late. Therefore, there is a need for other diagnostics methods. One of them may be a study of fluorescence spectra collected from tissue fragments which are used for histopathological examination. The phenomenon of fluorescence has been described accurately by physicists in the first half of the twentieth century. In recent years, you can see a number of applications of fluorescence spectroscopy in medicine, such as the DNA sequencing, the study of Alzheimer’s disease or intra-cellular processes. In rheumatology, with exception of immunofluorescence, tests using this method are rarely carried out. For this reason we decided to present an outline of the basics of fluorescence and its application in medicine, with particular emphasis on the applicability in the diagnostics of systemic connective tissue diseases. It turns out that the differences can be observed in the spectra of fluorescence, as is the case of cancer can be used to facilitate diagnosis of rheumatic diseases. Perhaps it will be another diagnostic method, which will allow faster diagnosis of the diseases and the introduction of proper treatment in their early stages.