Introduction: JC-polyomavirus-associated nephropathy (JC-PVAN) is a rare cause of allograft dysfunction with only a few cases described in the literature. Case Presentation: We present 2 cases of JC-PVAN, both of which occurred >5 years after kidney transplantation. In both cases, transplant biopsies were performed because of worsening of kidney function. We found tubulitis and interstitial inflammation; immunohistochemistry was positive for SV40, but BK virus was not detected. The presence of JC virus confirmed the diagnosis of JC-PVAN. Immunosuppressive therapy was adopted, but in both cases graft function progressively deteriorated. Conclusions: Our cases show that JC-PVAN, although much rarer than BK-PVAN, should be considered a possible cause of graft dysfunction even years after transplantation. Complete diagnostic workup, including kidney biopsy, is crucial for correct diagnosis and treatment.