Highly active antiretroviral therapy (HAART)-treated human immunodeficiency virus (HIV)-positive patients can develop granulomatous lesions within the first few weeks of initiating therapy. This immune syndrome, called immune restoration inflammatory syndrome (IRIS), can induce sarcoid-like lesions in tissues. The pathogenesis of these granulomas is currently unknown because no pathogen has been identified to date in the lesions using morphological and/or microbiological approaches. However, the role of certain microbes, such as Mycobacterium tuberculosis, is still debated. The aim of this study was to look for the presence of M. tuberculosis in sarcoid-like lesions occurring in 14 AIDS patients treated with HAART. We used the PCR DNA amplification method in granulomas microdissected from sections stained by hematoxylin-eosin from formalin-fixed, paraffin-embedded specimens. Results were compared to those obtained from microdissected tuberculosis (TB) granulomas (15 patients) and from microdissected sarcoidosis granulomas (12 patients). M. tuberculosis DNA was undetectable from the microdissected sarcoid-like granulomas, whereas DNA from M. tuberculosis was isolated in all the microdissected TB granulomas and was absent in the microdissected sarcoidosis granulomas. Taken together, these data showed that M. tuberculosis DNA is not associated with the presence of sarcoid-like lesions occurring in HIV-positive patients treated with HAART.