The case of an HIV-infected patient with low CD4+ cell count and localized pulmonary infection associated with Mycobacterium tilburgii, a recently recognized atypical mycobacterial species, is reported. Diagnosis was confirmed by repeated detection of mycobacterial DNA in lung biopsy specimens. After surgical removal of the pulmonary nodules, treatment with antimycobacterial combination therapy led to a complete and sustained recovery of the respiratory symptoms.M. tilburgii so far has only been described to cause disseminated infection in three patients, two of them suffering from acquired immunodeficiency syndrome. To our knowledge, this is the first report of localized pulmonary disease attributed to this mycobacterial species. As it responds to antimycobacterial combination therapy, efforts to establish the diagnosis using PCR methods in patients with suspected pulmonary disease due to mycobacteria other than tuberculosis should be undertaken.