Mucormycosis in two patients with multiple-organ failure appeared as a cutaneous lesion and spread rapidly. In the first case, wet mounts and potassium hydroxide preparations were unhelpful, but a punch biopsy specimen established the diagnosis. Prompt and extensive debridement and amphotericin B administration arrested the infection. In the second case, virulent progression of the lesion occurred despite limited amputation, debridement, transfer factor, and amphotericin B, but finally responded to further amputation. Diagnosis was made by histologic examination of infected tissue. Both patients shared the following predisposing factors: sepsis, low blood flow, acidosis, multiple-organ failure, and multiple-antibiotic therapy. Although the mucormycosis was controlled, as confirmed in the first case at autopsy and in the second case by clear margins following reamputation, the outcome was fatal in both cases due to other features of multiple-organ failure.