In order to monitor treatment response and enable individual, targeted therapy decisions for cancer patients, a continuous genetic follow-up of tumor-specific alterations is needed. One possibility to retrieve such data is the so-called liquid biopsy, i.e. the analysis of circulating tumor cells (CTCs), which rarely appear in blood. Liquid biopsies offer a minimal-invasive method for successive analyses of tumor genomes during the course of a cancer disease. CTCs are shed from primary and/or metastatic cancers and can enter the blood circulation, and subsequently travel to distant organs and form metastases. Despite their great potential as a cancer biomarker a widespread use is limited mostly due to technological issues. In this study the potential of the Parsortix system for the isolation of CTCs was investigated. Different cancer cell lines and CTCs from six metastatic cancer patients were enriched using the Parsortix system followed by two different technologies for single-cell isolation. The isolated cells were analyzed using the next-generation sequencing based mFAST-SeqS protocol, which represents a quick and cost-effective tool for the assessment of tumor-specific aneuploidy.Using spike experiments with cell lines a high variability in combination with a vast contamination of blood cells was observed with respect to harvest and capture rates. Due to this high degree of contamination with other blood components in the eluate, CTCs had to be isolated for molecular genetic characterization using other methods. Nevertheless, genomic profiles from CTCs could be established using a combination of Parsortix system and a single cell capture method. Taken together, the Parsortix cell separation system is an effective pre-enrichment method for tumor cells, but cannot be used for an isolation of pure CTC populations, which is though absolutely necessary for a better understanding of tumor heterogeneity.