In conclusion, we demonstrated that the combination of CTC immunoisolation and gene expression analyses represents an adequate strategy to: a) identify highly specific and sensitive CTC biomarkers with independent diagnosis and prognosis value and potential applicability in the management of advanced NSCLC patients; b) reveals NOTCH1 as a conducting factor in the biology of EpCAM positive CTCs and a potential therapeutic target to impair metastasis dissemination in NSCLC. Here, EPCAM is linked to non-small cell lung carcinoma.