Background It has been reported that there are more circulating tumor cells (CTCs) in the pulmonary vein (PV) than in the peripheral blood; however, it is unclear whether the CTC count changes in the PV after resection of a lung lobe. Methods Thirty-three lung cancer patients were recruited for the study, including 17 who underwent lobectomy via video-assisted thoracoscopic surgery and 16 via open thoracotomy. Sixty-six blood specimens were sampled from the PV before the PV was interrupted and after lobectomy. The CTCs were quantified using the oHSV1-hTERT-GFP method. Results Before PV interruption, the CTC (pre-CTC) detection rate was 79.0% (26/33), the mean number of CTCs was 3.36 (median 2, range: 0-18), and there was no significant relationship between the pre-CTC count and clinical factors, such as histologic findings and pathological T stage (P > 0.05). After lobectomy, the CTC (post-CTC) detection rate was 100% (33/33), the average number of CTCs was 14.88 (median 11, range: 1-69), and the post-CTC count was significantly higher in patients in whom the PV was interrupted prior to the pulmonary artery (PA) than in patients in whom the PA was interrupted before the PV (P = 0.016). Overall, the CTC count was significantly higher following surgery (P < 0.001). Conclusion Post-CTC counts were significantly higher than pre-CTC counts, suggesting that surgical manipulation may potentially dislodge tumor cells into the PV. Interrupting the PV prior to the PA during lobectomy may prevent partial CTC entry into the circulation.