Twenty-four patients with cancer met predetermined criteria for a diagnosis of zygomycosis over a 10-year period at our institution. All had hematologic malignancy, and most had either neutropenia or steroid use as a risk factor. Pulmonary involvement mimicking invasive aspergillosis was the most common presentation, and dissemination was seen in 58% of patients on whom autopsies were performed. Three-fourths of the patients with pulmonary zygomycosis had pathogenic microorganisms other than zygomycetes isolated from respiratory specimens. The sensitivity of cultures in detecting zygomycetes from respiratory specimens was low. A culture positive for zygomycetes was typically a preterminal finding in the fatal, acute cases. Two-thirds of the patients died. Favorable outcome seemed to correlate with lack of pulmonary involvement, surgical debridement, neutrophil recovery, and a cumulative total amphotericin B dose of 2000 mg. Therapy with high-dose amphotericin B, combined with aggressive surgery and immune reconstitution, offers the best chance for survival of cancer patients with zygomycosis.