IgG4-related disease is an immune-mediated chronic inflammatory disease with fibrosis, which can affect almost all organs in the body. In a few cases, only a single organ is affected. The incidence of isolated IgG4-related mediastinal disease is even rarer. This article reports a rare case of isolated IgG4-related middle mediastinal disease and provides a detailed description of its diagnosis and surgical treatment. The patient had a good prognosis and did not receive any medication such as corticosteroids after surgery. Follow-up after 6 months showed no recurrence.