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Objectives: To evaluate the diagnostic yield and concordance of upper tract urothelial carcinoma (UTUC) grading between ureterorenoscopic biopsies and surgical resections. Materials and Methods: The nationwide Dutch Pathology Registry (nationwide network and registry of histo- and cytopathology in the Netherlands [PALGA]) was searched for UTUC-positive renal units (RUs) with histopathology excerpts from ureterorenoscopic biopsies and surgical resections, matched for laterality and localization of the tumor, from 2011 until 2018. The positive predictive value (concordance) of the biopsy grade with regard to the final grade according to the World Health Organization (WHO) 2004 classification was calculated. Results: A total of 1002 UTUC-positive rental units were included, of which 776 UTUC-positive RUs were graded according to the WHO 2004 classification in the ureterorenoscopic biopsy, the localization-matched surgical resection, or in both. The diagnostic yield of biopsies for a classifying diagnosis was 89% with a sensitivity for UTUC of 84%. In case of UTUC, the diagnostic yield for biopsy-based grading and staging was 97% and 72%, respectively. The concordance of high-grade biopsies with regard to the final histopathology was 97% and 62% for low-grade biopsies. Upgrading to final high grade occurred in 33% of the low-grade biopsies. Downgrading to final low grade occurred in 2% of high-grade biopsies. Conclusions: This is the first study to portray the limitations of ureterorenoscopic biopsies for UTUC in a nationwide cohort. The diagnostic yield of ureterorenoscopic biopsies for a classifying diagnosis is suboptimal, but the diagnostic yield for grading according to the WHO 2004 classification is high. Yet, a worrisome amount of ureterorenoscopic biopsies are upgraded with regard to the surgical resection. Consequently, one-third of patients, who qualify for kidney-sparing treatment according to one of the criteria recommended for risk stratification, might be stratified incorrectly. These findings stress the importance of a timely and stringent ureterorenoscopic follow-up after kidney-sparing surgery and highlight the need for improvements in the diagnostic approach to optimize the risk stratification. [ABSTRACT FROM AUTHOR]