Since the PD-1/PD-L1/PD-L2 axis plays a vital role in immune tolerance and T-cell exhaustion, having emerged as a target for breast cancer immunotherapy, we investigated the relevance of serum PD-L2 (sPD-L2) levels in feline mammary carcinoma (FMC), to validate its potential use as a diagnostic and/or prognostic biomarker, and as a future target for immunotherapy. This evidence concerns the gene PDCD1LG2 and breast cancer.