Background/Purpose: Enhanced Liver Fibrosis (ELF) test is derived from an algorithm of 3 serum biomarkers of fibrosis (i.e. tissue inhibitors of matrix metalloproteinases, hyaluronic acid and aminoterminal propeptide of type III procollagen); it has been suggested as a sensitive/predictive tool for liver fibrosis. Aim of the study was to evaluate whether ELF may help in differentiating primary Raynaud’s phenomenon (Rp) from very early Systemic Sclerosis (SSc) in a cross-sectional multi-center study. Methods: 110 consecutive adult subjects with “isolated” Rp (i.e. without any symptoms/signs suggesting a connective tissue disease) referring to 3 Italian Rheumatology Centers in approximately 6 months time were enrolled. Patients underwent as first screening nailfold capillaroscopy (NC) and were tested for anti-nuclear antibodies (ANA) by IFF and blotting and classified as primary Rp (pRp) (i.e. NC and ANA negative), very early SSc (i.e. ANA and NC positive), or Rp with NC or ANA positive. Patients with any other fibrosing disorder and treated with interferon were excluded. 15 limited cutaneous (lc)-SSc and 15 diffuse cutaneous (dc)-SSc with disease duration 5 years were also studied. ELF score was determined blindly by an independent commercial service (iQur, UK). Statistical analysis was performed by regression modelling this score as a function of the diagnosis and age. The discriminant performance was evaluate by ROC curve analysis adjusting for age. Results: 60 subjects had pRp (mean age 43.1 yrs), 35 had Rp with positive ANA only (mean age 43.6 yrs), 4 had Rp with NC scleroderma pattern only (mean age 38.2 yrs) and 10 had a diagnosis of very early SSc (mean age 59.7 yrs). There were significantly differences between ELF scores in subjects with pRp (mean 7.84) vs patients with very early SSc (mean 8.44), lc-SSc (mean 8.68) and dc-SSc (mean 9.00) (p 0.03, 0.001 and 0.0001 respectively). ELF score in pRp and Rp with positive ANA or NC scleroderma pattern only was not statistically different, although a progressive increase was observed (mean 7.84, 7.90 and 7.95 respectively). Considering patients with and without SSc, the area under the ROC curve was 0.7465 (CI 95%: 0.6578–0.8351). When adjusting for age the AUC for youngest patients was 0.77 and it significantly decreased for the older patients. A correlation was observed between ELF score and age. Conclusion: ELF score shows unbalanced fibrosis biomarkers in very early SSc; it may represent useful potential tool in identifying Rp associated with a scleroderma signature.