Isolated renal infections with fungal organisms of the class Zygomycetes are rare, but these infections are most frequently seen in patients who are immunocompromised. We report the case of a 45-year-old African American man who presented with symptoms of right-sided pyelonephritis, including fever, dysuria, and flank pain. The patient's history was significant only for sickle cell trait, and no evidence of immunosuppression was identified. Renal ultrasound imaging revealed a hypoechoic lesion in the superior pole of the right kidney, and the radiologic differential diagnoses included neoplasm, abscess, and infarct. Urine cultures were negative, but urinalysis showed white blood cells, which were too numerous to count. A computed tomography scan of the abdomen and pelvis performed 2 weeks after the initial presentation showed a slight increase in the renal mass, despite antimicrobial therapy, and a right nephrectomy was subsequently performed. On gross sectioning, an 8.5-cm well-circumscribed lesion was identified in the upper pole of the kidney. Microscopic sections showed extensive necrosis of the renal parenchyma, and, in areas of both infarcted and viable renal tissue, large, broad, aseptate fungal hyphae with irregular branching. Angioinvasion with associated thrombosis was seen in the renal tissue. The morphologic features of the organism were most compatible with that of a zygomycete. No evidence of disseminated fungal disease was identified on imaging studies. This case represents a successful outcome of a rarely reported isolated renal zygomycosis in a patient with no known underlying risk factors for the infection and illustrates the wide range of clinical presentations with which zygomycotic infections may present. Copyright © by the Southern Society for Clinical Investigation.