Traditional nonoperative diagnostic approaches to the indeterminate solitary pulmonary nodule include bronchoscopy and percutaneous needle biopsy. Although both methods are minimally invasive, the diagnosis of the small, peripheral nodule may remain elusive. Open thoracotomy is often required when these methods fail to obtain a diagnosis. Between January 1991 and June 1992, 242 patients with indeterminate solitary lung nodules underwent thoracoscopic excisional biopsy as the primary diagnostic method. Wedge excisions of the nodules were all performed by thoracoscopic techniques using an endoscopic stapler alone (72%), neodymium:yttrium-aluminum garnet laser (18%), or both (10%). A definite diagnosis was obtained in all patients. Two patients required conversion to thoracotomy to locate the nodule (both malignant). A benign diagnosis was obtained in 127 patients (52%) and a malignant diagnosis in 115 (48%). Of the malignant nodules, 51 (44%) were primary lung cancer and 64 (56%) were metastases. All patients diagnosed with primary lung cancer having adequate pulmonary reserve (n = 29) underwent formal open lung resection during the same procedure. There was no mortality, and significant morbidity was limited to atelectasis in 3 patients (1.2%), pneumonia in 2 patients (0.8%), and prolonged air leak more than 7 days in 4 patients (1.6%). Average hospital stay for patients having thoracoscopy only (n = 213) was 2.4 days (range, 1 to 12 days). Thoracoscopy offers a minimally invasive approach for the diagnosis of the indeterminate solitary nodule. It has advantages over traditional diagnostic methods of being virtually 100% sensitive and 100% specific with no mortality and minimal morbidity.(ABSTRACT TRUNCATED AT 250 WORDS)