Limited information is available regarding the pathogenesis and clinical manifestations of infection with Cunninghamella bertholletiae. In this report, we describe the clinical courses of three patients with leukemia and fatal C. bertholletiae infection and review the literature. In all patients, the infection developed in the setting of severe neutropenia following high doses of cytotoxic chemotherapy. Clinical presentation always consisted of fever and pneumonia and could be associated with dissemination to numerous organs. The course of infection was very rapid, and the diagnosis was made around or after the time of death. The most important risk factors for C. bertholletiae infection described in the literature include corticosteroid administration and prolonged severe granulocytopenia. Four infectious syndromes due to Zygomycetes have been described: rhinocerebral, pulmonary, cutaneous and soft tissue, and disseminated. The outcome of disseminated infection with C. bertholletiae has been almost uniformly fatal. Most previously described patients, however, did not receive aggressive treatment consisting of amphotericin B administration, resection of infected tissues, and, most importantly, control of the underlying disease.