In the endemic area of tuberculosis, there are many cases that present tuberculosis as a solitary pulmonary nodule (SPN) on chest radiographs. The objective of this study is to evaluate the diagnostic yield of transbronchial lung biopsy (TBLB) under fluoroscopic guidance in SPNs such as lung cancer or pulmonary tuberculoma in areas with high prevalence of tuberculosis. One hundred and seventy patients with SPNs on chest radiographs were included in the study; all had negative sputum smears for tubercle bacilli and no malignancy by sputum cytology before bronchoscopy. Transbronchial lung biopsy and brushing were performed, routinely, under fluoroscopic guidance. Of 170 patients, 120 (70.6%) had lung cancer (including three with metastatic cancer), 40 (23.5%) patients had pulmonary tuberculosis (Tb), and the remaining 10 (5.9%) patients had other benign pulmonary lesions. The overall diagnostic rate in SPNs was 62.4% (106 of 170). Transbronchial lung biopsy and brushing revealed a diagnostic sensitivity of 70.0% in lung cancer (84 of 120) and a sensitivity of 55% in Tb (22 of 40). In addition, TBLB and brushing also provided rapid microscopic identification of Tb in 18 of 40 patients (45%, including 15 by TBLB, one by brushing smear, and two by postbronchoscopic sputum). The percentage of positive diagnosis correlated with diameter of the SPN. Solitary pulmonary nodules with diameter less than 2 cm were diagnosed in only 35.3% of cases (6 of 17; cancer 40% vs. Tb 29%). In contrast, the diagnostic rates in SPNs with diameters 2-4 cm and greater than 4 cm were 64.5% (78 of 121; cancer 72.0% vs. Tb 62.5%) and 68.8% of cases (22 of 32), respectively. Diagnostic bronchoscopy under fluoroscopic guidance is a useful tool in evaluation of patients with a peripheral pulmonary nodule since it may provide additional information to minimize unnecessary thoracotomy and give way for proper medication as early as possible.