Fine-needle biopsy and large-needle core biopsy of inaccessible and deep-space lesions of the head and neck are difficult and sometimes hazardous to perform. Patients subsequently may have to undergo a major surgical procedure with exploration of the neck and open biopsy. We describe our experience with computed tomography and ultrasound-guided fine-needle and core-needle biopsy for 11 patients with inaccessible lesions in the head and neck. Carcinoma was diagnosed in three patients and nonmalignant pathologic findings in eight patients. Three of the needle biopsy findings were confirmed by surgical excision. The initial diagnoses made from the cytopathologic findings have remained unchanged in all patients. Compared with the alternative of open biopsy, we have found this method to be technically easy, diagnostically expeditious, and safe. Head and neck surgical oncologists should be familiar with image-guided biopsy techniques, since many of their patients may benefit from these diagnostic procedures.