A 16-day-old premature male infant developed rapidly expanding necrotic facial plaques. Histology and cultures of tissue biopsy specimens revealed infection with Rhizopus arrhizius. The patient was treated aggressively with surgical debridement, amphotericin B, and rifampin, but had a progressive spread of the cutaneous infection and a fatal clinical course. He had gastrointestinal and pulmonary involvement on autopsy. Zygomycoses are rapidly progressive infections which generally affect immunocompromised hosts. Premature infants should be included as individuals at risk for disseminated zygomycotic disease.