Background: Testicular germ-cell cancer is curable even in the presence of metastatic disease. Yet, about 10-15% of patients become cisplatin-refractory and will eventually die of their disease. Moreover, short- and long-term side effects of cisplatin make the search for less toxic treatment strategies worthwile. Programmed Death Receptor 1 (PD-1, CD279) is one member of the extended family of T cell regulators expressed on the surface of activated T cells, B cells, and macrophages. Its ligand, PD-L1 (B7-H1, CD274), is expressed on tumor cells, T cells and other tissues. The interaction of these two molecules negatively regulates immune responses. Of major interest is that inhibition of the interaction between PD-1 and PD-L1 can enhance T-cell responses in vitro and mediate clinical antitumor activity. The aim of this study was to analyze the expression of PD-L1 in testicular germ-cell tumors to evaluate its potential as predictive marker for further therapeutic strategies. Methods: Immunohistochemistry was performed in 486 Formalin Fixed Paraffin Embedded (FFPE) specimens using a monoclonal rabbit antibody (E1L3N, Cell Signaling Technology, Inc. (CST) of Danvers, MA, USA). Results: PD-L1 expression was found in 171 out of 248 (69%) seminomas, 19 out of 48 (40%) yolk sac tumors, 7 out of 46 (15%) teratomas, 2 out of 10 (20%) choriocarcinomas and 53 out of 87 (61%) embryonal carcinomas. In 20 out of 20 Intratubular germ-cell neoplasia unclassified (IGCNU) and also in 20 out of 20 normal tissue specimens no single case exhibited PD-L1 expression. Conclusions: Our study describes for the first time the frequent expression of PD-L1 in a large series of human testicular germ-cell tumors, but not on normal testis tissue or IGCNU. Based on our results, checkpoint inhibition with anti-PD1 and anti-PDL1 antibodies might represent an attractive approach in germ-cell cancer, where new active agents are urgently needed.