We report the first two cases of invasive human mycoses caused by the phaeoid ascomycete, Chaetomium perlucidum, and review the English literature regarding invasive Chaetomium infections. Fatal disseminated disease involving the brain, heart, lungs, and spleen is described in an acute myelogenous leukemia patient. A second patient with a history of asthma and chronic bronchiectasis experiencing right-middle-lobe syndrome grew C. perlucidum from lung tissue. This study adds C. perlucidum to the list of other known neurotropic Chaetomium species, C. atrobrunneum and C. strumarium, and also documents this organism's ability to disseminate beyond the central nervous system.