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Solitary rectal ulcer syndrome (SRUS) often goes unrecognized or is misdiagnosed. Of 98 patients with a final clinicopathologic diagnosis of SRUS, an initially incorrect diagnosis had been made in 25 patients (26 percent). In these 25 patients with a misdiagnosis, the median age was 43 years and the female-to-male ratio was 3.2:1. The median duration of incorrect diagnosis was five years (range, three months to 30 years), and seven patients received prednisone (>30 mg/day) for a mistaken diagnosis of inflammatory bowel disease. The main clinical symptoms were rectal bleeding (84 percent) and a disturbance of bowel function (56 percent). Rectal prolapse was present in 13 patients. Original rectal biopsy specimens from 23 patients were reviewed; inadequate specimens and failure to recognize diagnostic features of SRUS contributed to delayed diagnosis in 13 and 10 patients, respectively. The most common clinicopathologic mis-diagnoses in SRUS patients with rectal ulcers or mucosal hyperemia were Crohn's disease and mucosal ulcerative colitis. In patients with “polypoid” SRUS, diagnostic confusion was usually with a neoplastic polyp. Persistent bowel symptoms and rectal lesions led to review of the presentations and repeat biopsy directed toward the edge of the rectal ulcers or from within the polypoid or hyperemic rectal lesions, finally establishing the diagnosis of SRUS. Intractable symptoms led to surgery in 15 patients (60 percent), with symptomatic improvement in over two-thirds.