Programmed death ligand-1 (PD-L1), a promising antitumor target, has proven clinical value against many malignancies. However, the PD-L1 content of Xp11.2 translocation renal cell carcinoma (Xp11.2 RCC) and its correlation with clinical outcomes remain unclear. This study aimed to investigate PD-L1 expression in Xp11.2 RCC and to assess its prognostic value. Formalin-fixed paraffin-embedded specimens from 36 adult patients that were histologically confirmed (by fluorescence in situ hybridization) were subjected to immunohistochemical analysis. Of the 36 Xp11.2 RCC patients, 9 (25.0%) had tumors with positive PD-L1 expression and 27 (75.0%) had tumors with negative PD-L1 expression. Positive PD-L1 expression correlated with advanced tumor stage (P = 0.001), regional lymph node metastasis (P < 0.001), and distant metastasis (P < 0.001). A multivariate analysis identified positive PD-L1 expression was an independent adverse prognostic factor for both progression free survival (hazard ratio: 3.7, P = 0.018) and overall survival (hazard ratio: 4.5, P = 0.034). Renal cell carcinoma (RCC) is widely recognized as a heterogeneous disease with various histological subtypes. The most common histopathological subtypes are clear cell (60%-75%), papillary (10%-15%), chromophobe (5%), and collecting duct carcinomas 1 . Xp11.2 translocation RCC (Xp11.2 RCC) is a rare subtype that was recognized as a distinctive pathological entity in the 2004 World Health Organization renal tumor classification 2, 3 . Xp11.2 RCC is characterized by several translocations on chromosome Xp11.2, resulting in gene fusion between TFE3 and at least six possible partners [4][5][6] .As it is a rare RCC subtype, the best treatment for Xp11.2 RCC has not been defined. Surgery is the optimal treatment for localized Xp11.2 RCC patients, including those with positive regional lymph nodes 7 . However, previous studies indicate that Xp11.2 RCC presents at an advanced stage with a rapid clinical course 8,9 . As a result, systematic treatment may be indispensable for most patients. Anti-VEGF drugs are reported to have activity against metastatic Xp11.2 RCC 10, 11 . However, Xp11.2 RCC has poor prognosis regardless of treatment 12,13 . Therefore, new, effective treatments are desperately needed for patients with this tumor type.Monoclonal antibodies (mAbs) targeting the programmed death 1 (PD1)/programmed death ligand-1 (PD-L1) pathway have achieved impressive response rates in patients with melanoma, non-small cell lung cancer, and bladder cancer, and PD-L1 has been validated as a predictive biomarker for the outcome of mAb therapy in many studies [14][15][16] . However, its prognostic and clinical value in patients with Xp11.2 RCC subtypes is unknown. In this study, we sought to investigate the levels of PD-L1 expression and its correlation with clinical outcome in a series of patients with Xp11.2 RCC that was histologically confirmed using TFE3 break-apart fluorescence in situ hybridization (FISH).