Resection of indeterminate pulmonary lesions in patients with a history of malignancy is indicated, as the presence of metastases will provide prognostic information and often dictate further therapy. Pulmonary metastasectomy also improves survival in select patients with favorable tumor histologies. We reported the results of video-assisted thoracoscopic surgery (VATS) resection of indeterminate lung nodules in 72 patients with a history of malignancy. All lesions identified on preoperative high-resolution CT scan were found at surgery with visual inspection, digital palpation, or (in 13 cases) CT-guided needle localization. All lesions were resected anatomically with a rim of normal parenchyma, as is done with open techniques; 63 patients were found to have metastases and 9 patients had benign disease. There was no mortality, minimal morbidity, and decreased hospital stays in patients undergoing VATS resection compared with historical control subjects. These data and other reports have led to the widespread use of VATS for patients undergoing resection to establish a diagnosis. The role of VATS in patients with favorable tumor histology and limited tumor burden for whom metastasectomy may result in a survival advantage remains controversial. Improved image resolution with spiral CT scans and digital palpation, combined with intraoperative ultrasound examination of the lung, may decrease or eliminate the number of lesions missed with a VATS approach. The role of therapeutic VATS metastasectomy remains to be defined. Thus, this procedure currently should be used only in clinical trials.