© American Society for Clinical Pathology, 2018. All rights reserved. Objectives Immune checkpoint therapy has been promising in renal cell carcinoma, but no validated clinically relevant biomarkers exist. Metastatic deposits may have discordant biomarker expression. Methods Fifty matched pairs of primary and metastatic kidney tumors were evaluated via immunohistochemistry for immune checkpoint proteins PD-1, PD-L1, and PD-L2 and the T-cell and macrophage surface markers CD3, FOXP3, and CD163. Semiquantitative scores incorporating prevalence of both tumor and nontumor labeling were compared between metastatic and primary kidney tumor specimens. Results A large minority of patients had discordant expression of PD-1 (31.2%), PD-L1 (22.5%), or PD-L2 (21.5%) between primary and metastatic sites. The expression of the novel marker PD-L2 correlated with both PD-1 (r = 0.47, P =.02) and PD-L1 (r = 0.67, P <.001) in metastatic deposits. Conclusions This study demonstrates that renal clear cell carcinoma primary tumors and metastatic deposits have some discordance in the expression of PD-L1, PD-1, and PD-L2.