AIM: To determine the prevalence of increased intraepithelial lymphocytes, using immunohistochemistry in patients with normal colonoscopy and near normal biopsy. METHODS: We retrospectively reviewed all non-malignant colon mucosal biopsies between 2005 and 2007, reported as normal, chronic inflammation or melanosis coli in patients who were undergoing routine colonoscopy. Immunohistochemistry using CD3 was performed on all mucosal biopsies and an intraepithelial lymphocyte count (IEL) was determined. Cases with an IEL count of ≥ 20 IELs per 100 surface epithelial cells were correlated with demographic, clinical and follow-up data. A further subgroup was evaluated for lymphocytic colitis.RESULTS: Twenty (8.3%) of 241 cases revealed an IEL count ≥ 20. Six (2.5%) patients were identified as having lymphocytic colitis (P < 0.001), of whom, five were missed on initial evaluation (P = 0.01). Four of these five patients were labeled with diarrhea-predominant irritable bowel syndrome (IBS). On follow-up, three of the remaining 20 cases were diagnosed with malignancy (renal cell carcinoma and myelodysplastic syndrome) and one had an unknown primary tumor with multiple liver metastases. Two cases of collagenous colitis with an IEL count < 10 were included in this study. Increased IELs were not confined to patients with diarrhea as a primary presenting symptom, but were also present in patients with abdominal pain (n = 7), constipation (n = 3) and loss of weight (n = 1). CONCLUSION: Immunohistochemistry using CD3 is of value in identifying and quantifying IELs for the presence of microscopic colitis in patients with diarrheapredominant IBS. METHODS: We retrospectively reviewed all non-malignant colon mucosal biopsies between 2005 and 2007, reported as normal, chronic inflammation or melanosis in Patients who were undergoing routine colonoscopy. Immunohistochemistry using CD3 was performed on all mucosal biopsies and an intraepithelial lymphocyte count (IEL) was determined. Cases with an IEL count of ≥ 20 IELs per 100 surface epithelial cells were correlated with demographic, clinical and follow- A further subgroup was evaluated as having lymphocytic colitis (P <0.001), of whom, Four were missed on initial evaluation (P = 0.01). Four of these five patients were labeled with diarrhea-predominant irritable bowel syndrome (IBS) Of follow-up, three of the remaining 20 cases were diagnosed with malignancy (renal cell carcinoma and myelodysplastic syndrome) and one had an unknown primary tumor with multiple liver metastases. Two cases of collagenous colitis with an IEL count <10 were included in this study. Increased IELs were not confined to patients with diarrhea as a primary presenting symptom, but also also present in patients with abdominal pain (n = 7), constipation (n = 3) and loss of weight (n = 1). CONCLUSION : Immunohistochemistry using CD3 is of value in identifying and quantifying IELs for the presence of microscopic colitis in patients with diarrheapredominant IBS.