Objective: We sought to determine the importance of histopathological assessment in patients with chronic diarrhoea who had macroscopically normal colonic endoscopies. Methods:Of 300 consecutive patients undergoing colonoscopy by one endoscopist during a five year period, biopsies were taken in 200 cases of unexplained diarrhoea of at least 6 weeks and their colorectal mucosa appeared macroscopically normal. All biopsies were reviewed by one pathologist. Results:Of the 200 patients enrolled, 36 (18%) cases were classified as unremarkable histopathological diagnosis and 164 (82%) cases showed histopathological changes: 121 (73.78%) non-specific inflammation, 19 (11.58%) ulcerative colitis, 11 (6.7%) collagenous colitis, 7 (4.26%) lymphocytic colitis, and 6 (3.65%) bilharzial colitis. Conclusion:We conclude that the role of biopsies in chronic diarrhoea patients with grossly normal colon at endoscopy is high as yielding a histological diagnosis in 21.5% of patients is so benefit to them as they may had modified the therapy received after identification of a specific cause as collagenous colitis, lymphocytic colitis, ulcerative colitis and bilharzial colitis. So Patients should be subject to colonoscopy and biopsy to aid specific diagnoses.