This study aimed to evaluate the efficacy of CT-guided core needle biopsy (CNB) in the diagnosis of deep head and neck tumors in untreated patients. We retrospectively reviewed the records of ten consecutive CT-guided CNB procedures from ten patients without a related history from March 2004 to February 2012. The surgical results, treatment response and clinical follow-up were used as the diagnostic standards. All specimens were considered adequate. Nine out of ten cases matched the final diagnosis. Biopsy failed to diagnose the infratemporal meningioma en plaque in a particular case. Three cases were carcinomas. No complication was encountered. CT-guided core needle biopsy is an efficient and safe technique for histological diagnosis of skull base lesions in patients without a related history. This technique can offer a definite tissue diagnosis and avoid unnecessary surgical interventions for such patients.