Chronic renal dysfunction is common in non-renal solid organ (SOT) and hematopoietic stem cell transplant (HSCT) recipients and is commonly attributed to calcineurin inhibitor toxicity, often without renal histopathologic evaluation. Polyomavirus nephropathy (PVN) is an important cause of allograft dysfunction in kidney transplant recipients but has rarely been reported in native kidneys of non-renal transplant recipients. We report the clinical, pathologic and virologic features of PVN in native kidneys of two allograft recipients. In both, severe renal dysfunction was accompanied by histopathologic evidence of PVN, including characteristic viral inclusions by routine stains, immunohistochemistry and electron microscopy. High levels of BK virus (BKV) DNA were detected in kidney tissue of patients using BKV-specific polymerase chain reaction (PCR). In 1 patient, high levels of BKV DNA were detected in plasma and urine, and administration of low-dose cidofovir was associated with clearance of BK viremia. These results extend the populations in which PVN has been documented in native kidneys to include heart and stem cell transplant recipients, and suggest that cidofovir has activity against BKV in vivo. Studies to define the incidence and potential contribution of PVN to chronic renal dysfunction commonly attributed to calcineurin inhibitor toxicity in non-renal transplant recipients are warranted.