Abstract Circulating tumor cells (CTCs) are important clinical indicators of metastatic progression and treatment efficacy. However, because of their low number and heterogeneity, reliable patient‐derived CTC models are not readily available. We report here the isolation and characterization of the invasive population of CTCs, iCTCs, from blood of 10 patients with epithelial ovarian cancer (EOC) and one pancreatic cancer patient based on the avidity of tumor cells toward an artificial collagen‐based adhesion matrix (CAM), in comparison with tumor progenitor (TP) cells isolated from tumor cell lines, tumors and ascites from EOC patients. CAM‐avid cells identified to be iCTCs were indistinguishable with TP cells using either functional CAM uptake or surface markers (seprase and CD44). In addition, iCTCs were characterized using peritoneal and spontaneous metastasis models in vivo to evaluate their metastatic propensity and therapeutic response. TP cells and iCTCs had a doubling time of about 34‐42 hours. TP cells were rare (