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Feature Editor Note—In this Invited Expert Opinion article, Wakeam and colleagues review the basic science of circulating tumor cells in non–small cell lung cancer in light of a recent randomized study from Wei and colleagues on the impact of a vein-first versus artery-first surgical lobectomy technique on circulating tumor cells and survival recently published in the Journal of the American Medical Association Surgery. The group at University of Michigan has expertise in the isolation of circulating tumor cells using intraoperative aspiration from the pulmonary vein. The potential effect of circulating tumor cells on survival is crucial, since 90% of all cancer-related deaths are thought to be due to metastatic disease. Circulating tumor cells may also serve as a prognostic and therapeutic biomarker. Wei and colleagues hypothesized that ligating the pulmonary veins first would help prevent shedding of circulating tumor …