Post transplant malignancy morbidity and mortality are important limitations in kidney transplantation. The incidence of malignancy has been estimated at 20% after 10 years of chronic immunosuppression. This retrospective study aimed to evaluate the benefit of switching from calcineurin inhibitors (CNIs) to sirolimus in post transplant malignancies. Six renal allograft recipients (4/2, m/f) of mean age 40 (25-56) years and mean time after transplantation of 54 ± 33 (11-108) months were switched to sirolimus-based immunosuppression abruptly, because of the presence of biopsy-proven malignancy. (3β cell lymphoma, 1 Kaposi sarcoma, 2 non melanoma carcinoma of skin). The mean follow up after sirolimus conversion was 8.5 ± 3.8 (4-12) months. Only one patient with lymphoma and CNS metastasis was on chemotherapy. The mean of creatinine before and after switching was 1.5±0.5 and 1.2±0.2 mg/dl, respectively. All patients had good cancer evolution after one month with no new tumor during follow up. In conclusion, sirolimus provide a potential treatment option in the management of post transplant malignancies and should be considered for use in renal transplant recipients who develop the disease.