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INTRODUCTION: Accurate histopathologic diagnosis of colorectal adenocarcinoma is important for treatment decision-making. The aim of this study was to measure rates and predictors of false-negative biopsy specimens attained at flexible endoscopy, and to determine whether these events led to delays in surgical care. METHODS:This was a retrospective cohort study of patients who underwent elective resection for colorectal cancers at a tertiary hospital in Canada. Primary outcomes were proportion of incorrectly diagnosed colorectal adenocarcinomas at index endoscopy by histopathology, and time between endoscopy and surgery. Secondary outcomes include predictors of sampling error, and diagnostic yield of repeat endoscopy.RESULTS: There were 961 patients who underwent elective resection for colorectal adenocarcinoma from 2007-2020. False negatives occurred in 217/961(22.6%) flexible endoscopies. Negative biopsies were associated with a longer median time to surgery (87.6 days, interquartile range [IQR]:48.8-180.0) compared with true-positive biopsies (64.0 days, IQR:38.0-119.0). Controlling for lesion location, neoadjuvant therapy, specialty, year, and repeat endoscopies, time to surgery remained 1.40-fold longer (p<0.001) after sampling error. Repeat endoscopies occurred after 62/ 217(28.6%) false-negative biopsies, yielding a correct diagnosis of cancer in 38/62(61.3%). On multivariate analysis, sampling errors were less likely to occur for lesions that endoscopists described as suspicious for malignancy (odds ratio [OR] 0.12, 95%CI 0.07-0.21) or simple polyps (OR 0.24, 95%CI 0.08-0.70) compared with endoscopically unresectable polyps.CONCLUSION: Colorectal cancers are frequently improperly sampled, leading to surgical delays. When cancer is suspected, endoscopists should take care to properly biopsy tumors at the index procedure to ensure timely management.