Cunninghamella bertholletiae is a rare cause of pulmonary mucormycosis. We describe a cluster of invasive pulmonary infections caused by C. bertholletiae in 4 immunocompromised patients that occurred during a 2-year period at 1 center. Three of the patients were receiving antifungal prophylaxis with itraconazole. Presenting symptoms were fever unresponsive to antibacterial chemotherapy, hemoptysis, and infiltrates on chest radiograms. Three patients were treated with liposomal amphotericin B. Only 1 patient survived.