BACKGROUND: Systemic sclerosis is clinically heterogeneous, presenting challenges in diagnosis and treatment. ANA testing, especially positivity for the Topo I nuclear pattern, is commonly part of the diagnostic process for systemic sclerosis as it aids in identifying the presence of the disease. Additionally, anti-Scl-70 antibody is a specific serological marker for systemic sclerosis, positively correlating with disease severity and activity. This report explores the clinical characteristics and treatment strategies of patients with systemic sclerosis who are Topo I nuclear pat-tern positive and anti-Scl-70 antibody negative. METHODS: Antinuclear antibodies (ANA) were detected using indirect immunofluorescence (IIF), and autoantibodies were detected using immunoblotting. Patients with IIF positivity and immunoblotting negativity for anti-Scl-70 antibody were analyzed. RESULTS: The patient was clinically diagnosed with systemic sclerosis. Laboratory tests showed ANA Topo I nuclear pattern positivity at 1:640, while anti-Scl-70 antibodies were negative. CONCLUSIONS: Patients with systemic sclerosis who are anti-Scl-70 antibody negative but Topo I pattern positive may present different clinical manifestations and prognoses, requiring a comprehensive assessment that integrates clinical presentation, laboratory tests, and potential disease progression.