Circulating tumor cells (CTCs) have emerged as a new generation of liquid biomarker that allows for noninvasive longitudinal disease monitoring. CTCs represent a rare cell population in the blood, surrounded by billions of hematopoietic cells. Due to the rarity of CTCs in the blood, the isolation of pure CTCs' populations has proven to be challenging. However, a number of new technologies have emerged using CTCs cytometric/immunological and physical characteristics. Currently, patients with

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... ter than 5 CTCs have a shorter progression-free survival, as compared with those with less than 5 CTCs per 7.5 ml of whole blood. Although the CTC count itself is an independent prognostic marker, the field is shifting toward understanding metastasis-relevant marker expression on CTCs for the improvement of the prognostic significance of CTCs. This chapter first introduces the principles of CTC isolation and detection methods, then the clinical utility of CTCs for prediction of prognosis and therapy response. Lastly, the heterogeneity of CTCs will be discussed.