During the past decade, polyoma virus (PV) infection has emerged as an important cause of graft dysfunction and failure in kidney transplant recipients. Establishing the correct diagnosis can be difficult, however, because the histologic appearance of PV infection can resemble acute cellular rejection. We report a kidney-pancreas transplant recipient with PV infection, in whom both vascular and cellular rejection were dominant histologic features in a renal biopsy specimen. The patient was successfully managed by tapering immunosuppressive therapy, and continues to have good graft function 3 years after diagnosis of PV infection. This case highlights the spectrum of inflammatory changes associated with PV infection, and the need for caution when such changes are attributed to rejection.