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Although urine cytology is used for the early detection and surveillance of urothelial carcinoma, there has been little study of the frequency, causes, and outcomes of cytologic-histologic discrepancies. We obtained histologic follow-up in 361 (6.2%) of 5,785 voided, 124 (19.5%) of 636 lower tract instrumented, and 23 (33%) of 69 upper tract urinary cytologic specimens from 1 institution during a 2-year timeframe to determine diagnostic discrepancy frequency and outcomes. Cytologic-histologic discrepancies were observed in 208 (40.9%) cases with histologic follow-up, and the cause of discrepancy was interpretation and sampling in 35.1% and 63.0%, respectively. Of all discrepancies, 101 (48.6%) resulted in minimal or mild harm, consisting mainly of repeated testing and/or diagnostic delays. Severe harm never was observed. We conclude that current screening and surveillance methods that incorporate urine cytology are accurate in diagnosing urothelial cancer. However, the current protocols result in potentially reducible errors that lead to unnecessary testing and diagnostic delays.