The authors report a case of a 35-year-old man with acquired immunodeficiency syndrome (AIDS) and a left colonic mass with Histoplasma capsulatum (H. capsulatum). The look-up performed looking for disseminated infection was negative. In the absence of positive cultures, the diagnosis was determined morphologically based on the presence of yeast observed by light and electron microscopy. The diagnosis was also verified by positive immunofluorescence using specific anti-Histoplasma antibodies. Gastrointestinal histoplasmosis is a frequent complication of AIDS, particularly in some endemic areas of America. Association with a disseminated mycotic infection is then common. Histoplasmosis is less frequently diagnosed in Europe and isolated involvement of the colon is exceptional. When the mycological study is not performed or is negative, only morphological and immunohistochemical methods are able to establish the diagnosis and eliminate other mycotic diseases occurring during AIDS.