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Background Colonoscopy is part of the current diagnostic armamentarium. However, in some patients with chronic diarrhea, a colonoscopy may show normal mucosa; in these cases, serial biopsies can provide important information for the diagnosis and treatment of patients. Aim To analyze patients with chronic diarrhea having a macroscopically normal colonoscopy, by evaluating histological changes. Methods 30 patients with chronic diarrhea and normal colonoscopy were prospectively evaluated and submitted to serial biopsies of the terminal ileum, ascending colon and rectum. Results The sample of 30 patients showed a ratio of 18 men (60%) and 12 women (40%). On histological types, it was found that 13 patients (43.3%) had lymphoid hyperplasia, eosinophilic inflammation in 4 (13.3%), nonspecific inflammation in 4 (13.3%), regenerative changes in 3 (10%), lymphocytic colitis in 2 (6.6%) and changes consistent with Crohn's disease in 1 (3.3%). Conclusions One can observe that even chronic diarrhea patients, without other associated factors, benefited from colonoscopy with biopsy, because it held the etiologic diagnosis in some cases as also excluded by histopathology. It was noticed that the frequency of patients with altered biopsy and less dragged diarrheal episodes (84.2%) was large, should consider their achievement.