Immune-Oncology (IO) has been rapidly changing the therapeutic landscape and the natural history of metastatic renal cell carcinoma (mRCC). Nevertheless, in mRCC G3-G4 Immune-Related Adverse Events (irAEs) develop in 1.7–19% of patients treated with anti-PD1 and 1.3–10.4% of patients treated with anti-PD1+anti CTLA-4 with consequent treatment interruption.