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Objectives To explore variations in disease presentation between isolated systemic sclerosis (SSc), primary biliary cholangitis (PBC) and SSc–PBC overlap syndrome.Design Systematic review conducted according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines.Setting Literature search of PubMed, Scopus and Google Scholar for studies published through June 2025.Participants 13 studies (from 1331 initially identified records) including patients with isolated SSc, isolated PBC and SSc–PBC overlap were included. Eligible studies were case–control or cohort designs reporting demographic, serological or clinical outcomes.Interventions Not applicable.Main outcome measures Differences in clinical phenotype, serological markers, systemic involvement and mortality between SSc–PBC overlap and isolated disease groups.Results Patients with SSc–PBC overlap demonstrated distinct clinical characteristics compared with isolated disease phenotypes. Anticentromere antibody and antimitochondrial antibody positivity were significantly higher in overlap patients. The overlap group predominantly included patients with limited cutaneous SSc and had a higher prevalence of extrahepatic autoimmune diseases, particularly Sjögren’s syndrome and Hashimoto’s thyroiditis. Systemic involvement, including pulmonary, musculoskeletal and cardiac manifestations, was less pronounced in overlap patients compared with isolated SSc. Liver-related mortality was higher in the PBC-only group, whereas mortality in the overlap group was primarily attributable to SSc-related causes.Conclusions SSc–PBC overlap syndrome represents a distinct clinical and immunological entity. Recognition of this phenotype may facilitate earlier diagnosis, guide management strategies and improve patient outcomes.