Computed tomography guidance enables deep neck biopsies beyond the range of ultrasound and spares the patient more invasive open surgery. This review article describes proper patient preparation, devices, and techniques. Cases illustrate the favored access routes in the suprahyoid neck including the subzygomatic, retromandibular, transfacial, submastoid, transoral, and posterior approaches, as well as in the infrahyoid neck including the anterolateral and posterolateral approaches. A thorough understanding of the neck anatomy, assessment of prior imaging with respect to eloquent structures such as arteries and nerves, and a sound knowledge of the technique will result in an extremely low complication rate.