Objective: Video-assisted lobectomy is an increasingly used technique to treat patients with non-small cell lung cancer but it does not usually afford lung palpation. Methods: A prospective study was conducted on patients with tumors amenable to video-assisted lobectomy (noncentral lesion and <5 cm) who underwent open lobectomy via thoracotomy. All patients underwent 64-slice helical computed tomographic scan with intravenous contrast at 5-mm intervals and had integrated 2-deoxy-2-18F-fluoro-d-glucose positron emission tomography computed tomography 30 days or less before thoracotomy. Unsuspected malignant pulmonary nodules that were palpated and removed (from a different lobe than the one resected) and that were not imaged preoperatively were defined as cancer that would have been missed by video-assisted lobectomy. Results: From January 2006 to February 2007, 166 patients had non-small cell lesions that were resected via thoracotomy, despite being amenable to video-assisted surgery, by one surgeon. Thirty-seven (22%) patients had pulmonary nodules that probably would have been missed by video-assisted lobectomy; 14 (8.4%) of these nodules were malignant. These were unsuspected M1 pulmonary lesions in 9 patients and unsuspected different types of primary non-small cell lung cancers in 5 patients. All missed lesions were less than 6 mm and in different lobes from the one resected. Nine (64%) of these 14 patients' primary known lesions were pathologic T1 lesions. Nine patients received adjuvant chemotherapy because of these unsuspected M1 nodules. Conclusions: Open lobectomy that affords palpation of the rest of the lung may discover nonimaged malignant pulmonary nodules in different lobes in 8% to 9% of patients with non-small cell lung cancer despite preoperative fine-cut chest computed tomographic scan with contrast and integrated integrated 2-deoxy-2-18F-fluoro-d-glucose positron emission tomography computed tomographic scanning. The clinical impact of these findings is unknown. © 2008 The American Association for Thoracic Surgery.