Objective: To evaluate the feasibility and performance of ultrasound-guided transcutaneous tru-cut biopsy (USGTCB) in selected patients (with stenosis of airways or difficult intubation or contraindication to general anaesthesia) with untreated or previously treated suspicious laryngo-hypopharyngeal masses. Methods: Biopsies were performed with a free-hand technique by a single radiologist. Thirty-six USGTCBs were scheduled in 34 patients (24 males, 10 females; age range 47-95 years). Two USGTCBs were not performed, as lesions were not detectable: therefore, 16 USGTCBs were performed for an untreated mass suspicious for malignancy and 18 were performed for a mass suspicious for recurrence after radiotherapy alone, or associated with endoscopic laser surgery or chemotherapy. Results: USGTCB diagnosed 25 squamous cell carcinomas (73.5%) and nine benign lesions (26.5%); no false positives and two false negatives were reported, both in patients previously treated with radiotherapy. The sensitivity, specificity, positive and negative predictive value of the technique was 92.5%, 100%, 100% and 77.7% respectively, with no major complications. Conclusion: Although biopsy under microlaryngoscopy remains the "gold-standard" technique, USGTCB is feasible, carries the advantages of avoiding general anaesthesia, is suitable for outpatients and is cost-effective. If applied to selected patients, it could be considered for the histological diagnosis of both primary and recurrent laryngo-hypopharyngeal masses.