A 69-year-old man, who had been receiving prednisolone for 11 months for treatment of interstitial pneumonia, was diagnosed with acute myeloid leukemia. During induction therapy, he developed severe pneumonia. Although meropenem and micafungin were started, he died of circulatory failure owing to massive gastrointestinal bleeding. Autopsy specimens obtained from the stomach revealed fungal hyphae, which had invaded diffusely into submucosal vessels and caused the massive gastric bleeding. The same hyphae were also observed in both lungs. A diagnosis of disseminated zygomycosis was confirmed by its characteristic histopathological findings. Because zygomycetes are spontaneously resistant to the newer antifungal agents, such as voriconazole or micafungin, it seems likely that the prevalence of zygomycosis as a breakthrough infection may increase in the future. Zygomycosis is a rare, but life-threatening, deep fungal infection that appears in immunologically or metabolically compromised hosts. Its manifestations are clinically similar to those of invasive aspergillosis. In addition to the well-established epidemiology of zygomycosis, this case suggests the following new characteristics. (1) Although the gastrointestinal manifestation of zygomycosis is relatively rare, it is observed more frequently than invasive aspergillosis. (2) Gastrointestinal zygomycosis occasionally leads to the development of necrotic ulcers and may induce hemorrhagic shock.(3) We should be cautious of an occurrence of breakthrough zygomycosis when we use echinocandins for patients with known risk factors, especially steroid use and neutropenia. (4) For patients who are receiving broad-spectrum antibiotics and echinocandins, who are negative for culture studies and aspergillus antigen, and who present with unresolved fever, it is important to make a prompt clinical diagnosis of zygomycosis.