BACKGROUND Immunoglobulin (Ig) G4-related disease is a rare disease of unknown pathophysiology, which can affect multiple organs leading to tissue fibrosis and organ failure. The present case report describes a patient with systemic IgG4-related disease (IgG4-RD) that occurred over a 1-year period and affected multiple organs at different times. Imaging studies, interventional procedures, changes in laboratory parameters, and histopathology demonstrate the novel and known aspects of this disease before and during prednisolone monotherapy and in combination with azathioprine. CASE REPORT A 64-year-old man presented with weight loss and painless jaundice, which was highly suspicious for cholangiocarcinoma. A thorough medical history together with laboratory tests, imaging procedures, and endoscopic interventions confirmed that surgery was not needed and led to the final diagnosis of histologically-confirmed, IgG4-related sclerosing cholangitis and autoimmune pancreatitis type 1. Other typical organ manifestations of systemic IgG4-RD were diagnosed through a thorough medical review, which led to immunohistochemical reevaluation of past surgical specimens. Besides the IgG4-related organ manifestations, which can include periorbital xanthelasmas, our patient developed a pulmonary adenocarcinoma 6 years after the initial clinical onset of IgG4-RD. After immunosuppressive treatment with prednisolone alone and subsequently in combination with azathioprine, the patient’s IgG4-RD resolved. CONCLUSIONS Interdisciplinary collaboration is required to diagnose IgG4-RD that involves multiple organs. Patient medical history remains crucial for diagnosis and attention should be paid to avoiding unnecessary surgery. Tumors (lung adenocarcinomas) and xanthelasmas can develop because of IgG4-RD. Glucocorticoids and additional azathioprine may be advisable for maintenance treatment.