Currently, there are no clinical or laboratory measures that accurately predict progression of skin fibrosis and organ involvement in patients with systemic sclerosis (SSc). The goal of this study is to identify skin biomarkers in early diffuse cutaneous SSc patients, to prognosticate the progression of skin fibrosis. We found that skin gene expression of biomarkers associated with macrophages (CD14, IL13RA1) and TGFβ activation (SERPINE1, CTGF, OSMR) are prognostic for progressive skin disease. These biomarkers might help to guide decisions about which patients should be considered for aggressive therapies and/or for clinical trials. Overall design: We analyzed clinical data and skin biopsy gene expression from 42 placebo patients, part of the Roche faSScinate phase 2 study of tocilizumab in SSc. RNA samples were analyzed using nCounter technology. A trajectory model, based on the modified Rodnan skin score was used to describe three skin disease trajectories over time. We examined the association of skin gene expression with trajectory groups of skin score using the Chi-square test. We used logistic regression to examine the prognostic power of each gene identified.