We report a patient with multifocal fibrosclerosis presenting as sialadenitis, hepatic fibrosis, and retroperitoneal fibrosis with renal failure. His medical management consisted of prednisone (4 months at 40 mg daily, then tapered down to 5 mg daily for another 14 months) and 18 months of tamoxifen. He responded clinically and radiographically to this regimen, and remains in clinical remission 10 months after discontinuing medical therapy. Subsequent histologic examination of submandibular gland tissue revealed strong staining for IgG4-positive plasma cells. To our knowledge, this is the first case of confirmed multifocal hyper-IgG4 disease to be successfully treated with sequential corticosteroids and tamoxifen.