High prevalence of tuberculosis increases the odds for nonmalignant solitary pulmonary nodules (SPNs). Positron emission tomography (PET) using (18)F-fluorodeoxyglucose is the method of choice for the identification of malignant SPNs requiring curative surgery. However, PET is not widely available. Technetium-99m methoxy isobutyl isonitrile (MIBI) is inexpensive, widely available and shows increased uptake in malignant SPNs. The aim of the present study was to prospectively evaluate the diagnostic value of MIBI single photon emission computed tomography to distinguish between benign and malignant SPNs in a tuberculosis-endemic area. In total, 49 patients with radiologically indeterminate SPNs (single lesion < or =6 cm in diameter) were prospectively evaluated with MIBI. The final diagnosis was established with bronchoscopy, fine-needle aspiration, surgical resection or clinical follow-up for > or =2 yrs. A total of 12 (92%) out of 13 malignant lesions showed increased uptake of MIBI, while no uptake was observed in 33 (92%) out of 36 benign lesions. MIBI uptake indicated malignancy with a sensitivity and specificity of 92% and a negative predictive value of 97%. In this tuberculosis-endemic area, technetium-99m methoxy isobutyl isonitrile single photon emission computed tomography evaluation of solitary pulmonary nodules had a high negative predictive value. Therefore, it has the potential to prevent unnecessary surgical resections of benign nodules and serve as a low-cost alternative when positron emission tomography is not available.