Background: Rhinocerebral zygomycosis is a rare, rapidly progressive and often fatal fungal infection occurring in several immunocompromised states. Prior investigators have reported an increasing incidence among Iranian population; therefore, we decided to present the clinical features and treatment outcome of a group of patients with rhinocerebral zygomycosis.Patients and methods: Medical records of all cases with the diagnosis of rhinocerebral zygomycosis attending Rasoule-Akram Hospital, Tehran, Iran, were retrospectively reviewed from 1997 to 2007. Age, gender, predisposing illness, surgical procedures, and treatment outcomes were reviewed.Results: Totally, 30 patients (17 males and 13 females) were reviewed with a mean age of 49.4±20.3 years. The lag time between onset of symptoms referable to zygomycosis and commencement of amphotericin B was 1 to 90 days with median of 10 days. An association between delayed treatment and mortality was found (p=0.01). Visual loss was observed in 53.3%. The ethmoid (86.6%) and maxillary sinuses (66.6%) were most commonly involved. Eighteen patients had underlying diabetes mellitus (60%). All patients received medical treatment, while 28 (93.3%) underwent surgical intervention. Twenty three patients (76.7%) had orbital involvement with a mortality rate of 43.5%. The overall mortality rate was 40% (12 cases). Patients with higher doses of amphotericin B and multiple surgical intervention had lower mortality rate (p=0.00 and p=0.01, respectively). Factors such as age, gender, predisposing diseases, orbital involvement, multi-sinus involvement, and white blood cell count had no impact on survival rate.Conclusion: Institution of aggressive surgical debridement of devitalized tissue and the timely initiation of systemic medical therapy is critical for good outcome.