Progress in diagnostic radiology and pathology during the past decade has changed the approach to diagnosis of mediastinal masses. Diagnosis by CT-guided needle biopsy (CTNB) has replaced open biopsy and mediastinoscopy, CTNB of mediastinal masses is accurate, reliable and safe. It is done under local anesthesia, in ambulatory patients and is tolerated well. Between July 1987 and April 1997 we performed 67 biopsies in 63 patients aged 6-86 years; 33 were women (average age 40.8 years) and 30 men (average age 38.3 years). 57 of 67 biopsies were core biopsies for histologic examination and 10 were cytologic biopsies. In this report we concentrate on the 57 core biopsies. 41 of the biopsies were diagnostic; in 3 of them no evidence of malignancy was found. In 38 of the biopsies a tumor, malignant or benign, or an inflammatory process was diagnosed. In 24 of the biopsies the diagnosis was lymphoma. In 16 there was not enough material for diagnosis. We repeated the biopsy in 4 of the latter due to high suspicion of malignancy and reached a diagnosis in all 4 of them. In 6 the diagnosis was reached only on operation. The biopsies were from all compartments of the mediastinum. There were no complications such as pneumothorax or bleeding, except for 1 case of mild hemoptysis. In conclusion, CTNB of mediastinal lesions is accurate, safe and relatively cheap. In 72% a diagnosis was reached in the first attempt and a second attempt raised the diagnostic rate to 79%. We believe that CTNB should be the first step in tissue diagnosis of mediastinal masses, including those under high suspicion of lymphoma.