Abstract The long-term effects of cancer on patient quality of life and its economic burden are important issues that need to be addressed. Therefore, it is critical to assess patient priorities and investigate the value proposition of clinical tests in this field. The minimally invasive liquid biopsy has attracted much attention because it allows serial sampling during cancer progression, and provides valuable biological information on the tumor biology and treatment response through the analysis of analytes in the blood, such as circulating tumor cells (CTCs). To introduce CTC analysis in daily clinical practice, it is still necessary to firmly establish its clinical benefits and extra value for clinical decision-making. A laboratory medicine value proposition of CTC medical applications can help to address these issues. In this review, we discuss the current evidence for a value proposition of CTC detection, isolation, and characterization using the available technologies, and we summarize the unmet requirements for the full integration of CTCs in the care pathway.