4565 Background: Sarcomatoid differentiation in metastatic RCC (sRCC) is associated with poor prognosis. Robust data regarding outcome in the targeted therapy era is lacking. Methods: Clinical features, prognostic factors, and treatment outcomes in mRCC patients with and without sarcomatoid histology treated with targeted therapy were retrospectively analyzed and compared. Results: 2,286 patients were identified (non-sRCC(n=2,056); sRCC(n=230)). sRCC patients had significantly worse Heng prognostic group distribution compared to non-sRCC (11% vs 19% favorable risk, 49% vs 57% intermediate risk, and 40% vs 24% poor risk; p<0.0001). Time from original diagnosis to relapse (excluding synchronous metastatic disease) in the sRCC patients was 18.8 months compared to 42.9 months in non-sRCC group; p<0.0001. There was no significant difference in the incidence of CNS metastases (6-8%) or underlying clear cell histology (87-88%). Greater than 93% of patients received VEGF inhibitors as first line therapy; 21% achi...