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An office-based workup strategy for patients with laryngopharyngeal lesions suspicious for carcinoma is analyzed. The feasibility of office-based transnasal flexible endoscopic biopsies under local anesthesia and the impact on the diagnostic workup are evaluated.This study is a prospective analysis of patients with laryngeal, oropharyngeal, and hypopharyngeal lesions suspicious for carcinoma. One hundred eighty-eight participants were divided into 2 groups. The first group underwent an office-based biopsy procedure under local anesthesia using a flexible digital video laryngoscope with instrument channel (n = 53), and the second group underwent a biopsy procedure under general anesthesia using rigid laryngopharyngoscopy (n = 135).Office-based flexible endoscopic biopsies were tolerated well, and there were no complications. These biopsies were 92.5% successful in acquiring a definitive diagnosis. Costs were reduced. Diagnostic workup time and time until start of therapy were reduced to 2 days and 27 days, respectively.Office-based biopsy under local anesthesia using flexible digital video laryngoscopy is safe, cost-effective, and successful in providing a histopathological diagnosis. It reduces the diagnostic workup time significantly in patients with laryngeal, oropharyngeal, and hypopharyngeal cancer, while also reducing the necessity to subsequently perform a rigid laryngopharyngoscopy under general anesthesia.