 However, the disease-free time to progression was still less than 1 year in most study.3-5 More than half of patients acquired resistant by new EGFR T790M resistance mutation. A second biopsy at the time of progression is becoming an issue. However, Only around 30 of NSCLC patients can receive gene testing to predict target therapy response because of the risk and difficulty in obtaining adequate tissues from the primary lung tumors by biopsy. Serial monitoring the emergence of resistant mutations is almost not possible. Recently, circulating free DNAs cfDNAs become a promising topic in cancer research. cfDNA can be used as a liquid biopsy, allowing repeated blood samples to be taken and changes in mutation status to be tracked throughout a cancer treatment, paving the way for a potential use in following up of treatment response, gauging prognosis, or monitoring of recurrence.6 It has been known for over a hundred years that disseminated tumor cells can be found in the circulation of patients with metastatic cancer and it has been hypothesized that these circulating tumor cells CTCs may represent cancer stem cells or a high metastatic potential cellular population.7 The major challenge since as few as one CTC may be found in the background of 105-106 peripheral blood mononuclear cells.8 CTCs are an attractive alternative to tumor tissue for biomarker analysis including EGFR mutation. CTCs can be obtained from a routine blood draw with minimal risk and inconvenience to the patient compared to a fresh biopsy. Another appealing facet of CTCs as a surrogate diagnostic tissue is the idea that CTCs could also constitute a liquid biopsy like cfDNA and provide real-time information about the patients current disease state.9,10 Analysis of biomarker status in CTCs collected prior to treatment could potentially be used to select an appropriate targeted therapy, while repeated longitudinal sampling during treatment could be used to detect appearance of resistance markers and potentially enable switching to a more appropriate therapy. 