Rhinocerebral zygomycosis was classically associated with diabetes and diabetic ketoacidosis in the past. In recent years, hematological malignancies and immunocompromised states have become increasingly more frequent underlying conditions for patients with pulmonary and disseminated zygomycosis. In this study we identified 37 patients with a histopathologic diagnosis of zygomycosis and 21 patients with a positive culture for zygomycetes seen at the National Taiwan University Hospital, Taipei, during 1986-2003. Of these, 39 cases with probable or proven invasive zygomycosis were included in these studies. The major underlying diseases were immunocompromised states (74%), and diabetes mellitus (26%). The frequency of zygomycosis in immunocompromised hosts increased from 1.86 during 1986-1991 to 4.13 per 100,000 discharges during 1998-2003. Rhinocerebral involvement was the most common site (74%). An antemortem diagnosis by sinus biopsy was made in 93.1%. Immunocompromised patients were more likely to be younger than diabetics, to have an onset during hospitalization, a positive culture and a postmortem diagnosis. They were less likely than patients with diabetes to receive surgery and more likely to die in the hospital (p < 0.05). Of the 29 patients with invasive rhinocerebral zygomycosis, cerebral involvement (adjusted odds ratio [OR]: 31.7, 95% confidence interval [CI]: 2.4-426.8, p = 0.009) and positive cultures (adjusted OR: 23.8, 95% CI: 1.7-338.6, p = 0.019) were associated with in-hospital mortality by multivariate analysis. Hematological disease and steroid use have become the most important predisposing factors for zygomycosis. Aggressive diagnostic approaches, effective antifungal therapy and surgical debridement are essential for a successful outcome.