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Introduction. Due to the heterogeneous nature of systemic sclerosis, it is difficult to predict disease progression and complications. Despite the discovery of novel autoantibodies associated with systemic sclerosis (SSc), there is an unmet need for biomarkers for diagnosis, disease progression, and response to treatment. Materials and methods. An analytical, qualitative study was performed with a narrative review of literature in the form of a synthesis article. Relevant primary sources published in 2020-2022 were identified and selected, using data extraction and analysis. Results. Anti-citrullinated protein/peptide antibody could be useful in identifying patients with a more prominent joint disease. Of most interest, the anti-carbamylated protein antibodies (anti-CarP) could be a relevant biomarker related to fibrotic skin and lung disease. Positive anti-RNA (Ribonucleic acid) polymerase III antibody and antinuclear antibodies (ANA) negativity were significantly associated with GAVE (gastral antral vascular ectasia). Autoantibodies against telomeres may help identify systemic sclerosis with lung disease. Osteopontin links myeloid activation and disease progression in systemic sclerosis. CTRP (C1q tumor necrosis factor-related proteins) 9 protein levels may be biomarker of lung disease severity. CD (cluster differentiation) 21-low B cells are linked to vascular damage. L-tyrosine, L-tryptophan, and 1-methyl-adenosine distinguished healthy controls from SSc patients. L-leucine, L-isoleucine, xanthosine, and adenosine monophosphate differentiated between progressing and stable SSc-ILD. CECs (circulating endothelial cells) are a direct indicator of systemic vascular damage. Levels of the protein, galectin-3, are associated with heart involvement in people with systemic sclerosis. Low levels of the galectin-10 protein (Gal-10) in scleroderma patients associate with inflammation and vascular changes in the lungs, leading to pulmonary arterial hypertension (PAH). High levels of the CD146 protein may be a potential biomarker in identifying people with systemic sclerosis. Blood levels of the protein endocan increased in scleroderma patients who are at risk for pulmonary arterial hypertension. FLCs (free light chain) could be employed as useful potential biomarker of early diagnosis and to follow disease activity. Conclusions. Novel discovered biomarkers could predict disease development, activity, and severity of diverse organ involvement, predict risk of complications of systemic sclerosis.