BACKGROUND: Immunoglobulin G4-related disease (IgG4-RD) is characterized by the formation of inflammatory lesions with fibrosis and infiltration of IgG4-positive plasma cells and lymphocytes in various organs of the body. Since the first report of IgG4-related autoimmune pancreatitis, IgG4-RD affecting various organs has been reported; however, only a few reports of IgG4-related lung disease (IgG4-RLD) exist. In this report, we describe a case of IgG4-RLD that was difficult to differentiate from malignancy, and the usefulness of the surgical approach in determining the appropriate diagnosis and treatment plan. CASE PRESENTATION: A 61-year-old man was referred to our hospital after a chest radiograph revealed an abnormal chest shadow. At the time of his first visit, he had a slight fever and dyspnea on exertion. Chest computed tomography (CT) revealed a middle lobe hilar mass with irregular margins and swelling of the right hilar and mediastinal lymph nodes. These findings were not present on CT 1.5 years ago. 18F-fluorodeoxyglucose-positron emission tomography revealed a mass lesion with a maximum diameter of 5.5 cm, maximum standardized uptake value (SUVmax) of 11.0, and areas with high SUV in the hilar and mediastinal lymph nodes. We suspected lung cancer or malignant lymphoma and performed a thoracoscopic lung biopsy to confirm the diagnosis. Histopathological examination revealed no malignant findings, and IgG4-RLD was diagnosed. One month after treatment with prednisolone (PSL), the tumor had shrunk, but a CT scan during the third month of PSL treatment revealed multiple nodular shadows in both lungs. Considering the possibility of malignant complications and multiple lung metastases, we performed thoracoscopic partial lung resection of the new left lung nodules to determine the treatment strategy. Histopathological examination revealed no malignant findings in any of the lesions, and the patient was diagnosed with IgG4-RLD refractory to PSL monotherapy. CONCLUSIONS: IgG4-RLD refractory to PSL monotherapy showed changes from a solitary large mass (pseudotumor) to multiple nodules on chest CT. It was difficult to distinguish malignancy from IgG4-RLD based on imaging tests and blood samples alone, and the surgical approach was useful in determining the appropriate diagnosis and treatment plan.