Transbronchial lung biopsy through the flexible bronchoscope is used widely for the diagnosis of diffuse lung disease; however, a significant number of specimens obtained by the bronchoscopic 2-mm biopsy forceps will reveal nonspecific findings, eg, interstitial fibrosis or nonspecific pneumonitis. Such a report may be an accurate reflection of the presence of idiopathic pulmonary fibrosis or nonspecific pneumonitis, but may merely indicate that the true diagnosis has been missed. We retrospectively studied 38 patients with diffuse lung disease whose transbronchial lung biopsies yielded nonspecific abnormalities. Subsequently, these patients were subjected to open lung biopsies. Nineteen of the 38 patients (50%) had a specific diagnosis made by open lung biopsy. The diagnoses included bronchiolitis obliterans, alveolar proteinosis, metastatic carcinoma, lymphoma, tuberculosis, and bronchioloalveolar cell carcinoma. Although transbronchial lung biopsy is useful in the diagnosis of many diffuse lung diseases, it is not a replacement for open lung biopsy. When nonspecific findings by transbronchial lung biopsy do not correlate with the clinical picture, open lung biopsy should be performed.