A 41-year-old woman had noticed sclerodactyly for 9 months before consultation. She was diagnosed as having diffuse cutaneous systemic sclerosis based on the skin sclerosis of her extremities and trunk and assessed by the modified Rodnan skin score method. Her anti–topoisomerase I antibody (anti–topo I) level was 78.1 index (normal range, ≤16 index). With oral prednisolone treatment, her skin sclerosis gradually improved and disappeared. In parallel, her serum anti–topo I levels became undetectable. Prednisolone was eventually discontinued; however, 10 months after discontinuation, anti–topo I reemerged and increased to 102.1 index, accompanied by newly developed skin sclerosis. Prednisolone was re-started, and the skin sclerosis improved, along with a reduction in anti–topo I levels. Therefore, discontinuation of corticosteroids may have triggered the re-emergence of anti–topo I and skin sclerosis. This case suggests a role for anti–topo I in the pathogenesis of systemic sclerosis and an effect of corticosteroids on skin sclerosis and autoantibody production.