This report is the first, to the best of our knowledge, indicating that CD248, first identified as a tumor vascular endothelial antigen [35] and considered a key molecule of myofibroblast generation, is deeply involved in TGF-β and PDGF-BB signaling transduction during the fibrosis associated with SSc and that its inhibition strongly interferes with the profibrotic pathways of these two cytokines. The gene discussed is CD248; the disease is systemic sclerosis.