Simple Summary: The diagnosis of active neoplastic disease was traditionally judged an absolute contraindication for extracorporeal membrane oxygenator (ECMO) because of long-term results uncertainty and co-existing acquired coagulation disorders often diagnosed in this group of patients. There is a growing body of evidence that circulating tumor cells (CTCs) can be detected in the blood of patients before the primary tumor is diagnosed and in the case of carcinoma recurrence; moreover, on some occasions, they persist in the blood of patients after radical resection of the primary tumor. The aim of this prospective, two-arm study is to compare the number of CTCs before and after surgery in patients undergoing lung cancer resection with and without intraoperative ECMO support. Intraoperative ECMO for lung cancer resections did not impact CTC variation after the procedure and did not impact postoperative complications, ICU stay, hospital total length of stay, and post operative C-reactive protein increase. Background: The diagnosis of active neoplastic disease was traditionally judged an absolute contraindication for extracorporeal membrane oxygenator (ECMO) because of the fear of tumor cells being scattered or seeded. The aim of this study is to compare the number of circulating tumor cells (CTCs) before and after surgery in patients receiving lung cancer resection with and without intraoperative ECMO support. Methods: This is a prospective, non-randomized, two-arms observational study comparing the number of CTCs before and after surgery in patients receiving lung cancer resection with and without intraoperative ECMO support. The ECMO arm includes patients suffering from lung cancer undergoing pulmonary resection with planned intraoperative ECMO support. The non-ECMO arm includes patients suffering from non-early-stage lung cancer undergoing pulmonary resection without planned intraoperative ECMO support. Results: Twenty patients entered the study, eight in the ECMO arm and twelve in the non-ECMO arm. We did not observe any significant difference between the ECMO and non-ECMO groups in terms of postoperative complications (p = 1.00), ICU stay (p = 0.30), hospital stay (p = 0.23), circulating tumor cells' increase or decrease after surgery (p = 0.24), and postoperative C-reactive protein and C-reactive protein increase (p = 0.80). The procedures in the non-ECMO arm were significantly longer than those in the ECMO arm (p = 0.043). Conclusions: Intraoperative ECMO for lung cancer resections did not impact CTC increase or decrease after the procedure. [ABSTRACT FROM AUTHOR]