Lymphocytic and collagenous colitis are types of microscopic colitis (MC) that commonly cause chronic watery diarrhea, but there are no macroscopic features of MC that can be detected during colonoscopy. Endoscopists therefore often collect multiple random colonic biopsies, potentially oversampling, increasing times of colonoscopy and slide review. We sought to identify sites from which biopsies could be taken and analyzed to identify patients with MC with a high level of sensitivity and determine the appropriate number of biopsies to take at these sites. We performed a retrospective study using biopsies from 101 consecutive patients with MC (52 cases of collagenous colitis, 42 cases of lymphocytic colitis, 7 combined cases), without comorbidities, from 2017 through 2018. Slides were reviewed, and the proportion of biopsies that were diagnostic of MC were calculated at each biopsy site. The proportions of biopsy fragments from each site of the colon found to be positive for MC were as follows: cecum, 90.0%; ascending colon, 96.9%; hepatic flexure, 77.8%; transverse colon, 95.7%; splenic flexure, 75.0%; descending colon, 85.0%; sigmoid colon, 90.9%; and rectum, 82.2%. For biopsies labeled random, 95.7% were positive for MC. When findings from ascending and descending colon biopsies were combined, 100% of MC cases were detected. MC can be detected with certainty by analyzing biopsies from the ascending and descending colon. Fewer biopsies than were collected from our cases are sufficient for diagnosis. We propose a Western protocol (taking 2 biopsies from each of the ascending and descending colon) in evaluation of patients for MC. Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.