The CD274 (CD274 molecule, a.k.a. PDCD1LG1, PDL1) and PDCD1LG2 (programmed cell death 1 ligand 2, a.k.a. PDL2, CD273) genes, which are separated by 42 kilobases, are located on chromosome 9p24.1. The genes encode ligands for the PD-1 receptor of T-cells. CD274 is expressed by cancer cells of various tumor types, including melanoma, non-small cell lung cancer (NSCLC), breast cancer, and renal cell carcinomas. It is believed that interactions between the T-cell PD-1 receptor and its ligands CD274 or PDCD1LG2 expressed by tumor cells prevent the immune system from attacking the tumor cells. The blockade of the PD-1/CD274, PDCD1LG2 pathway has yielded promising results in clinical trials conducted on tumors that express the PD-1 receptor. In early phase clinical trials compounds blocking PD-1 and CD274 have shown to be especially effective in advanced-stage NSCLC patients positive for CD274. Hence, targeting PD-1 or CD274, PDCD1LG2 represents a promising new treatment for this cancer entity. Consequently, the identification of CD274,PDCD1LG2 gene copy number detected by Fluorescence in situ Hybridization might be of prognostic and predictive relevance in diverse cancers.