Although disseminated histoplasmosis is recognized as a common opportunistic infection in HIV-infected persons living in endemic areas, it is not widely reported in Southeast Asia, and has not been reported in Cambodia. It remains unanswered whether this is secondary to a low disease prevalence, or whether the disease, which is associated with a nonspecific clinical presentation, is under diagnosed. In addition to a review of the literature regarding histoplasmosis in Southeast Asia, we provide a description of two HIV-1 infected patients with documented disseminated histoplasmosis complicating other opportunistic infections in Phnom Penh, Cambodia. These two cases highlight the need for both a high clinical suspicion, and reliable laboratory testing, in a setting where there is likely to be more than one infection complicating the patient's clinical course.