Well-recognized risk factors for zygomycosis include diabetic ketoacidosis, immunocompromise, and deferoxamine therapy for iron or aluminum overload, usually in patients undergoing kidney dialysis. We report a case of fatal nasal-orbital-cerebral zygomycosis in an 82-year-old man with known myelodysplasia and well-controlled diabetes. He was not receiving deferoxamine. Despite radical surgery and amphotericin B therapy, he died; primary hemochromatosis with gross iron overload was found post mortem. Experimental evidence suggests iron overload without deferoxamine therapy may be a risk factor for zygomycosis; the findings in this case would support this hypothesis.