Tuberculosis/HIV-1 co-infection is responsible for thousands of deaths each year, and previous studies have reported that co-infected individuals display major morphological alterations in tissue granulomas. The purpose of this study was to evaluate immunohistopathological characteristics in lung tissues from pulmonary TB/HIV-1-co-infected individuals. Following autopsy, tuberculosis-positive HIV-1-negative cases displayed granulomas with normal architecture, mainly composed of a mononuclear infiltrate with typical epithelioid, as well as giant cells, and exhibiting caseous necrosis. In contrast, lesions from the TB/HIV-1-co-infected group showed extensive necrosis, poorly formed granulomas, and a marked presence of polymorphonuclear cells. More importantly, TNF staining was greatly reduced in the TB/HIV-1-co-infected individuals. Our data suggest that HIV-1 infection alters the organization of pulmonary granulomas by modulating TNF and, possibly, cell trafficking, leading to an impaired anti-tuberculosis response.