Chronic intestinal schistosomiasis (CIS) can mimic chronic colitis of other etiologies, particularly inflammatory bowel disease. Recognizing clinical and pathologic features unique to schistosomiasis can facilitate differential diagnosis. Clinical, endoscopic, imaging, macroscopic, and histologic features of 40 CIS cases were reviewed and compared with 40 cases of Crohn disease (CD). The most common symptoms of CIS were abdominal pain, distention, bloody stool, weight loss, and anemia. Lesions were mainly located in the rectum and/or left colon in 67.5% of patients. Polyps were seen colonoscopically in 57.1% and yellow granular hyperplasia in 40% of patients. Spotty or linear calcifications were radiographically seen in 21.7% of patients. Macroscopically mural thickening and stricture with erosions or ulcerations were seen in resected specimens of CIS. Four patients were initially diagnosed as having ulcerative colitis and 3 as CD (a misdiagnosis rate of 17.5%). The key microscopic feature was calcified ova in the submucosa, some accompanied by fibrosis, granulomas, or multinucleated giant cells. Crypt distortion, ulceration, and transmural lymphoid aggregates were less frequent in CIS than CD (P<0.05). Pyloric gland metaplasia was absent in CIS. Interestingly, eosinophilic counts were not significantly increased in tissue in CIS as compared with CD. Thus, clinical, endoscopic, imaging, and macroscopic manifestations are not specific for CIS. Correct diagnosis relies on increased awareness of this disease and rigorous search for parasitic eggs in tissue, particularly in patients from endemic areas who are suspected to have inflammatory bowel disease.