Retroperitoneal fibrosis, although histologically benign, has a malignant course due to encasement and compression of tubular retroperitoneal structures, particularly the urinary system. The etiology of this neoplastic process is unclear, but clinical symptoms result from fibroblast proliferation with excessive collagen deposition. Because of the diffuse nature of this disease, surgical resection is technically impossible, and past medical therapies have been inconsistent. Tamoxifen has been shown to be effective in the treatment of desmoid tumors, and we present a patient with retroperitoneal fibrosis who was treated successfully with this anti-estrogen. Because of its minimal side effects and simplicity of dosing, tamoxifen may be a useful treatment in this disease.