We report a case of a relatively large desmoid fibromatosis that responded completely to tamoxifen as a single drug therapy. A 47-year-old Japanese man underwent laparoscopy-assisted endoscopic submucosal dissection for a duodenal polyp. He developed postoperative generalized peritonitis and underwent an emergency laparotomy. Sixteen months after the surgery, a subcutaneous mass was found on the abdominal wall. Biopsy of the mass revealed estrogen receptor alpha-negative desmoid fibromatosis. The patient underwent total tumor resection. Two years after the initial surgery, he was found to have multiple intra-abdominal masses, with the largest mass measuring 8 cm in diameter. Biopsy revealed fibromatosis, as in the case of the subcutaneous mass. Complete resection was impossible due to the proximity of the duodenum and superior mesenteric artery. Tamoxifen was administered for three years, resulting in complete regression of the masses. No recurrence was observed for the following three years. This case indicates that relatively large desmoid fibromatosis can be successfully treated with a selective estrogen receptor modulator alone and that its effect is not dependent on the estrogen receptor alpha status of the tumor.