Aim: We report the outcomes observed with nivolumab in metastatic renal cell carcinoma patients with poor prognostic features enrolled in the Italian expanded access program. Patients & methods: Nivolumab was available for patients who relapsed after at least one prior systemic treatment in the advanced or metastatic setting. Results: Of 389 patients, 32 (8%) had brain metastasis, 129 (33%) had liver and 193 (50%) had bone metastasis. These subpopulations achieved a disease control rate of 53, 45 and 47%, respectively. Fifty-one patients had G4 tumor, and they showed 23% objective response rate. The safety profile of the subgroups was in line with the expanded access program population. No new safety signals were reported. Conclusion: Patients with poor prognostic features may derive relevant benefits from nivolumab.