Systemic sclerosis is an autoimmune inflammatory disorder of unknown etiologycharacterized b y pronounced fibroproliferative alterations in the microvasculature, and frequent cellular and humoral immunity abnormalities, culminating in a severe and often progressive fibrotic process. Numerous biomarkers reflecting the three main pathogenetic mechanisms in systemic sclerosis have been described; however, aside from several disease-specific autoantibodies, other biomarkers have not been thoroughly validated and require further study. Thus, there is an unmet need for validated biomarkers for diagnosis, disease classification, and evaluation of organ involvement and therapeutic response in systemic sclerosis.