The diagnosis of diffuse lung disease can only be made accurately by performing a thoracoscopic lung biopsy. We evaluated the safety and efficacy of thoracoscopic lung biopsy in diffuse lung disease. Between May 1999 and April 2003, 34 patients were referred to us for thoracoscopic lung biopsy. We compared the clinical characteristics, number of biopsies, operation times, postoperative course, complications, and mortality in 19 patients with dyspnea and 15 patients who were asymptomatic. Although the number of biopsies, operation times, duration of chest drainage, and postoperative stay did not differ significantly between the 2 groups, postoperative oxygen support was needed for significantly longer in the dyspnea group (p =0.038). A pathological diagnosis was established in all patients. Postoperative complications developed in 4 patients. A prolonged air leak in 1 patient and a wound infection in another resolved conservatively, but 2 patients died of acute exacerbation. Thus, we conclude that the indications for surgery must be carefully considered in dyspneic patients with diffuse lung to prevent acute exacerbation.