Background: CTCs have been widely used in monitoring the efficacy and prognosis of lung cancer. However, CTCs number count alone cannot accurately predict the recurrent disease in patients. In this study, we investigate whether the morphology classification of CTCs could be as a prognostic marker for increased risk of recurrence after surgery. Methods: In this study, 105 lung cancer patients (median age 68y) who underwent surgery were prospectively enrolled in this study. Samples were obtained before, after, and serially up to 24 months after surgery. CTCs were collected and morphology classified by utilizing a CTC test workflow which uses negative enrichment and immunofluorescence methods to capture and identify CTCs from blood sample. Captured CTCs (epithelial type) were screened with a customized imaging analysis pipeline, a cytological profile of each CTC was created, including cell size, shape, fluorescent intensity and texture etc. Results: The CTC detection rate was 78.1% (78 of 105) prior to surgery, and a total of 726 CTCs were enumerated. Median CTC count number was 3. 5 classes of CTCs with distinct morphological features were observed in lung cancer patients’ CTC tests, briefly, CTC class I and class II possessed large nuclei but relatively lower epithelial expression level, CTC class III, IV, V possessed small nuclei but relatively higher epithelial expression level, CTC class III possessed irregular shaped nuclei, CTC class V possessed relatively lower nuclei/cytoplasm ratio. Class III accounted for the highest proportion of captured CTCs III, about 35.5% with Class I 14.8%, Class II 15.3%,Class IV 17.8% and Class 5 16.6%. Postoperative recurrence and metastasis were observed in 16 patients. CTCs positive were found in 14 patients (87.5%). 145 CTCs were collected, Median CTC count number was 3,Cluster III accounted for 47.3%, with Class I 11.8%,Class II 13.3%,Class IV 14.5% and Class V 11.8%; Patients with Cluster 3 dominant were associated with increased risk of local recurrence (p < 0.05) and distant metastasis (p < 0.05). Conclusions: Small and irregular nuclei CTC is significant associated with increased risk of recurrence disease. Morphology Classification of circulating tumor cells is feasible in monitoring the recurrence of disease and may potentially identify the patients who may benefit from further therapy.