Abstract Objective: To assess the technique, efficacy, and safety of computed tomography (CT)-guided percutaneous biopsies of head and neck masses. Materials and Methods: This was a retrospective, single-center study of CT-guided percutaneous core-needle biopsies of head and neck masses. For the analysis of diagnostic accuracy, biopsy results were compared with the final diagnosis, which was determined by histological examination and clinical follow-up. Results: We evaluated 74 biopsies performed in 68 patients. The mean age of the patients was 55.6 years. Most of the lesions (79.7%) were located in the suprahyoid region, and the maximum diameter ranged from 11 mm to 128 mm. The most common approaches were paramaxillary (in 32.4%), retromandibular (in 21.6%), and periorbital (in 14.9%). Five patients (6.8%) developed minor complications. The presence of a complication did not show a statistically significant association with any clinical, radiological, or procedure-related factor. Sufficient material for histological analysis was obtained in all procedures. Thirty-eight biopsies (51.4%) yielded a histological diagnosis of malignancy. There was a false-negative result in three cases (8.3%), and there were no false-positive results. The procedure had a sensitivity of 92.7%, a specificity of 100%, and an accuracy of 96.0%. Conclusion: Our results demonstrate that CT-guided percutaneous core-needle biopsy of head and neck lesions is a safe, effective procedure for obtaining biological material for histological analysis.