Despite the reported value of assessing the overexpression of PD-L1 on cells of different types in solid tumors—including lung cancer—as a promising marker to predict anti PD-1/PD-L1 treatment efficacy, the predictive value of PD-L1 expression is still controversial and related investigations face the three major limitations of tissue biopsies: Invasiveness, sampling error due to tumor heterogeneity, and mostly unfeasible longitudinal sampling. The gene discussed is PDCD1; the disease is lung cancer.