BACKGROUND: Tuberculosis control hinges on prompt diagnosis of active cases and screening of contacts by tuberculin skin testing. Rapid blood tests for Mycobacterium tuberculosis infection are a new alternative to the tuberculin skin test, but whether they improve clinical outcomes is unknown. OBJECTIVE: To describe how a novel T-cell-based test for M. tuberculosis infection helped diagnose tuberculosis in an asymptomatic, immunosuppressed adult with a negative result on a tuberculin skin test. DESIGN: Case report. SETTING: Household contact. PATIENTS: Asymptomatic man receiving maintenance azathioprine therapy for Crohn disease whose wife had multidrug-resistant pulmonary tuberculosis. MEASUREMENTS: Enzyme-linked immunospot (ELISPOT) assay, computed tomography, and bronchoalveolar lavage cultures. RESULTS: The man had a negative tuberculin skin test result and a positive ELISPOT assay result. High-resolution computed tomography of the chest showed consolidation with early cavitation. Bronchoalveolar lavage and culture confirmed multidrug-resistant tuberculosis. LIMITATIONS: This single case report is a proof of concept and is not a formal evaluation of clinical utility. CONCLUSIONS: A positive ELISPOT assay result helped diagnose subclinical active tuberculosis in an immunosuppressed patient with a false-negative tuberculin skin test result. Large prospective studies that compare benefits and costs of this alternative to tuberculin skin testing are needed.