Background: PD-L1 expression on circulating tumor cells (CTCs) is an alternative to checkpoint inhibitor selection by IHC and it offers possibility for serial monitoring following chemotherapy, immunotherapy or radiation therapy. Here we report a sensitive technique to assess PD-L1 expression by CTCs for early and late stage lung cancer. Methods: Two mL blood from 40 patients diagnosed with NSCLC, as well as PD-L1 positive cell lines from lung and breast cancer were processed with the proprietary CMx microfluidic platform. This test captures EpCAM+ cells, which are subsequently confirmed as CTCs based on size, morphology and CK18+/CD45- staining. Expression of PD-L1 is assessed by staining intensity using PD-L1 monoclonal antibody BioINK with cutoffs established by negative control cells. Results: Cell lines showing heterogeneous expression levels for EpCAM, CK18 and PD-L1 reminiscent of CTCs were spiked into healthy donor bloods at various concentrations (10/30/90 per 2mL blood) and assessed for PD-L1 expression. Capture efficiency correlated with EpCAM expression levels and PD-L1 staining intensity levels were concordant with those reported in the literature. Circulating tumor cells were detected in 35/40 (88%) of NSCLC patients across Stages I-IV (range 1-32 CTCs; median 4 CTCs). CTCs were detected in 91% (21/23) of early, and 11/13 (85%) of late stage patients with known staging. 55% (22/40) patients were found to have at least one PD-L1 expressing CTC. IHC PD-L1 results were available in 28 NSCLC patients with detectable CTCs. The PD-L1 CTC assay was positive in 6/8 (75%) patients expressing high levels of PD-L1 by IHC, using the > = 50% cutoff for 1^st line immunotherapy selection, including two early stage patients. Importantly, 8 patients who were IHC negative were PD-L1 positive by the CTC test, including 5 early and 3 late stage patients. Conclusions: To the best of our knowledge this is the first study showing high sensitivity of CTCs in detecting PD-L1 in early stage NSCLC. This CellMax CTC blood test can be used for immunotherapy selection and treatment monitoring of NSCLC patients regardless of treatment modality or stage of cancer.