Immunoglobulin G4-related disease (IgG4-RD) is a recently defined condition characterized by inflammatory tumefactive lesions in various organ systems. IgG4-RD is a clinical and radiological diagnosis of exclusion and requires the presence of specific histopathological criteria for diagnosis. A 50-year-old man presented to an outside hospital with a 3-month history of progressively worsening back pain and symptoms of pleurisy, nasal crusting, and hematochezia. Radiological workup revealed an epidural-paraspinal mass with displacement of the spinal cord, destruction of the T5-6 vertebrae, and extension into the right lung. Biopsy sampling and subsequent histopathological analysis revealed dense lymphoplasmacytic infiltrate with an increased number of IgG4-positive plasma cells and a storiform pattern of fibrosis. With strong histopathological evidence of IgG4-RD, the patient was started on a regimen of prednisone. Further testing ruled out malignant neoplasm, infectious etiologies, and other autoimmune diseases. Two weeks later, the patient presented with acute-onset paraplegia due to spinal cord compression. The patient underwent decompression laminectomy of T5-6, posterior instrumented fusion of T2-8, and debulking of the epidural-paraspinal mass. After the continued administration of glucocorticosteroids, the patient improved remarkably to near-normal strength in the lower extremities and sensory function 6 months after surgery. To the authors' knowledge, this is the first case of IgG4-related epidural inflammatory pseudotumor and spinal cord compression in the United States. This case highlights the importance of early administration of glucocorticosteroids, which were essential to preventing further progression and preventing relapse. IgG4-RD evaluation is important after other diseases in the differential diagnosis are ruled out.