TNB of the mediastinum is an accurate, safe, and cost-effective diagnostic tool for the evaluation of mediastinal masses and lymphadenopathy. The technique is most useful in the staging of carcinoma, where it serves as a less expensive and minimally invasive alternative to mediastinoscopy for establishing unresectability. With recent advances in immunohistochemical and core biopsy techniques, TNB has become more accurate for establishing the initial diagnosis of lymphoma and for confirming recurrent disease. Core-needle biopsy has improved the accuracy of TNB and is particularly useful when fine-needle aspiration fails to yield a specific diagnosis, or when lymphoma or a noncarcinomatous lesion is suspected.