Endobronchial ultrasound-guided transbronchial fine-needle aspiration (EBUS-FNA) is a minimally invasive method used routinely for mediastinal staging of patients with lung cancer. We have used it in 135 consecutive patients with a radiologically suspicious intrathoracic lesion that remained undiagnosed despite bronchoscopy and CT-guided fine-needle aspiration (CT-FNA). There was no operative mortality or surgical complications. In 98 patients with a suspicious lesion in the lung parenchyma, adequate tissue was obtained in 83 patients (85%) and in 37 patients with enlarged lymph nodes or a mediastinal tumor adequate tissue was obtained in 35 cases (95%). However, a final diagnosis was only reached in 45% of the patients and further investigations led to malignancy in 13. We believe that EBUS-FNA represents a good alternative to more invasive diagnostic procedures when conventional methods fail, even though the diagnostic yield is lower compared with mediastinal staging in patients with known lung cancer. In almost half of the cases, EBUS-FNA provides the final diagnosis without exposing the patient to the risk of complications from more invasive procedures.