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Background: In‐office biopsies (IOB) using local anaesthetic for laryngopharyngeal tumours has become an increasingly popular approach since the advent of distal chip endoscopes. Although a wide range of studies advocate use in clinical practice, the widespread application of the procedure is hampered by concerns regarding diagnostic accuracy. Objective: To assess the diagnostic accuracy of IOB performed via flexible endoscopy. In addition, to analyse modifiable factors that may affect diagnostic accuracy of IOB. Design: A systematic review following the PRISMA guidelines was conducted. PubMed, EMBASE, the Cochrane Library, Web of Science and CINAHL were used in the literature database search. Quality assessment of included studies was perfomed using the Newcastle‐Ottawa Scale. Results: A total of 875 studies were identified, 16 of which were included into the systematic review; 1572 successful biopsies were performed using flexible endoscopy; 1283 cases were accurately diagnosed in the outpatient setting (81.6%) and 289 samples did not provide an accurate diagnosis (18.4%). The median sensitivity of IOB was 73%, and the specificity was 96.7%. Analysis of variable factors did not show any significant differences in method of approach, size of equipment (forceps) and additional lighting system or learning curve. Conclusion: IOB are a viable tool for diagnostic workup of laryngopharyngeal tumours. Clinicians should be wary of reported limitations of IOB when benign or pre‐malignant diagnoses are made. In cases suspicious of malignancy, confirmatory investigation should be conducted. [ABSTRACT FROM AUTHOR]