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At the time of diagnosis, systemic sclerosis (SSc) is often well established with significant irreversible tissue and organ damage. Definitions of ‘early SSc’ have been proposed, which include the presence of SSc-associated autoantibodies. In addition, functional autoantibodies that are believed to be involved in SSc pathogenesis need to be considered. In this review, recent advances in the diagnostic utility and pathogenic role of autoantibodies in early SSc are summarized. Moreover, we propose a clinical care pathway illustrating how autoantibody testing along with key clinical features can be used to make an earlier diagnosis of SSc.Recent evidence has helped to develop a clearer understanding of the natural history, early clinical features, and autoantibodies that are predictors of SSc. The role of functional autoantibodies is leading to innovative approaches to evidence-based interventions and therapies that are based on mechanisms of disease.Despite substantial advances, the high morbidity and mortality that currently characterizes SSc can largely be attributed to a delay in diagnosis, gaps in our understanding of the role of autoantibodies in early disease, and limited effective therapeutic options. An early and accurate diagnosis of SSc and use of autoantibody testing embedded in evidence-based clinical care pathways will help improve SSc-associated clinical outcomes and healthcare expenditures.