BackgroundThis study was conducted to investigate the correlation between clinicopathological features and post‐therapeutic response in esophageal squamous cell carcinoma (ESCC) patients. Peripheral blood circulating tumor cells (CTCs) expressing epithelial‐mesenchymal transition markers were identified.MethodsPeripheral blood samples were collected from 71 patients with newly diagnosed ESCC and 40 healthy volunteers. CTCs were isolated using CanPatrol CTC enrichment technology. RNA‐fluorescent in situ hybridization was used to phenotype the CTCs on the basis of epithelial and/or mesenchymal markers.ResultsThe median mesenchymal CTC counts in 71 patients were: 0 in 19 stage I patients, 2 in 31 stage II, and 3 in 21 stage III/IV. The overall diagnostic performance of total CTCs to correctly identify ESCC patients was 0.991. We observed a correlation between increases in tumor size or advanced stage and an increased number of mesenchymal CTCs (P < 0.05). Thirty‐nine patients were administered two cycles of neoadjuvant chemotherapy and their therapeutic response was evaluated: 2 complete response, 20 partial response, 13 stable disease, and 4 progressive disease. After treatment, the positive rate of mesenchymal CTCs was 70.6% in the progressive and stable disease group versus 36.4% in the complete and partial response group (P = 0.05).ConclusionThe results showed that mesenchymal CTC count is related to ESCC clinical stage and the efficacy of neoadjuvant chemotherapy.