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CyberKnife Frameless Image-Guided Stereotactic Radiosurgery with the Synchrony Motion Tracking Module is available for treatment of thoracic malignancies. Gold fiducials are used to mark the tumor site and have traditionally been placed through computerized tomographic (CT) guidance. We describe the first use of video flexible bronchoscopy with a modified transbronchial needle aspiration (TBNA) technique for placement of these fiducials. Fiducials were placed in the 19-gauge needle of a 19/21-gauge transbronchial needle. The 19-gauge fiducial-loaded needle was then retracted into the sheath and the sheath passed through a flexible bronchoscope. At the desired location, the 19-gauge needle was extended into the tumor. The 21-gauge needle was tightened and the fiducial deployed under fluoroscopic guidance. Between July 2004 and March 2005, 15 patients underwent fiducial placement through flexible bronchoscopy. Nonsmall lung cancer (NSCLC) was the most common diagnosis. A total of 54 fiducials were placed within the mediastinum and lung parenchyma. Complications related to the fiducials included: 1) 12 fiducials dropped in the airway before deployment, 2) migration of one fiducial, and 3) embolization of one fiducial through the pulmonary artery without adverse clinical consequence. There was no incidence of pneumothorax or significant bleeding. One patient developed bronchospasm after the procedure requiring mechanical ventilation. Flexible bronchoscopy with TBNA appears to be a safe method for the placement of fiducials for centrally located chest tumors.