IntroductionDifferentiation of tuberculoma from cancer in solitary pulmonary nodule or mass still remains a major challenge in diagnostic laboratories. ObjectivesThe objective of this study is to determine the performance of T-SPOT.TB assay in discriminating these 2 diseases. MethodsWe prospectively enrolled 331 patients with a solitary pulmonary nodule or mass on computed tomography scans. Conventional tests and T-SPOT.TB assay were simultaneously performed in all participants. ResultsOur results showed that the performance of directly using T-SPOT.TB results in distinguishing tuberculoma from cancer in solitary pulmonary nodule or mass was not satisfactory because of moderate sensitivity and specificity. However, a further calculation of the ratio of TB-specific antigen (TBAg) to phytohemagglutinin (PHA) (TBAg/PHA ratio) of T-SPOT.TB assay may lead to improvement in distinguishing these 2 diseases. If using the threshold value of 0.236, the sensitivity and specificity of the TBAg/PHA ratio in distinguishing tuberculoma from cancer in solitary pulmonary nodule or mass were, respectively, 80.6% and 93.3%. The area under the curve (AUC) of the receiver operating characteristic curve was 0.921 (95% confidence interval, 0.875-0.967). Furthermore, the TBAg/PHA ratio may also be used to distinguish tuberculoma from other benign diseases (AUC: 0.909, sensitivity: 85.07%, specificity: 90%). ConclusionsCalculation of the TBAg/PHA ratio might provide a useful non-invasive tool for distinguishing tuberculoma from cancer in patients with a solitary pulmonary nodule or mass in TB-endemic countries.