Renal transplantation provides the best quality of life for the patients with chronic end-stage renal failure. However, the immunosuppression necessary for graft survival may give rise to infectious complications, an increased risk of cardiovascular and neoplastic diseases, all of which can shorten the patient's survival. The objective of this study was to evaluate the efficacy and safety of the proliferation signal inhibitor immunosuppressant drugs everolimus among patients who develop neoplasms after renal transplantation. This retrospective study included 25 patients (mean age -56.5 +/- 14.1 years) who were diagnosed with posttransplant neoplastic disease and immunosuppressed with calcineurin inhibitors (CNIs). Treatment was initiated with everolimus with or without CNIs. During the follow-up, the renal function (initial serum creatinine 1.4 mg/dL vs final serum creatinine 1.3 mg/dL) and proteinuria levels (initial 0.3 g/d vs final 0.4 g/d) remained stable. There was a low percentage of patients with relapse of their tumor. One patient had a relapse of bladder cancer with tumor progression at 3 years; another patient with melanoma developed lymph node invasion. There were neither acute rejection episodes nor cardiovascular complications. The results suggested that tumor relapse was low. The results suggested that immunosuppression with everolimus combined with low doses of CNIs or in single-drug therapy is safe immunosuppression for patients who develop posttransplant malignant diseases.