BACKGROUND: A negative sputum smear from a patient with history, physical examination, and chest x-ray findings suggestive of tuberculosis (TB) presents a diagnostic dilemma. We investigated the possible factors associated with a misdiagnosis and inappropriate treatment of TB among such patients. METHODS: We reviewed the records of 193 patients whose diagnoses with TB included conflicting test results and were reported to the Taiwan Centers for Disease Control in 2004. When other conditions were found to underlie the initial abnormal chest x-ray finding, the diagnosis was revised. RESULTS: Mycobacterium tuberculosis was isolated from sputum samples in 72 of 193 patients (37%), nontuberculous mycobacteria from 4 (2%), and no bacteriologic evidence of M. tuberculosis from 117 (61%). The initial diagnosis of TB was revised for 26 (13.5%) patients. Patients with positive M. tuberculosis culture had a lower incidence of revised diagnoses (4.2%, P < .001) than those negative for mycobacterial culture (17.1%) and those with nontuberculous mycobacteria (75%). Chest cavitations in this study were not a significant predictor of revised diagnosis (odds ratio 0.30, P = .08). CONCLUSIONS: An incorrect diagnosis of TB despite a negative sputum smear result is more likely to be made for patients positive for nontuberculous mycobacteria culture and less likely for patients with positive M. tuberculosis culture.