Simple SummaryDielectrophoresis (DEP) is a label-free cell manipulation technique based on electrical differences that can be applied to liquid biopsies in the context of cancer prognosis and early diagnosis. In fact, it can overcome the current limitations of other platforms in detecting circulating tumor cells (CTC) in prostate cancer (PC), such as the low number of CTCs detected (less than one CTC/mL of peripheral blood), high-cost and time-consuming means for detection, quantification, isolation and characterization. The aim of this review is to give deep insights into the role of DEP for the diagnosis and prognosis of cancer.Liquid biopsy is emerging as a potential diagnostic tool for prostate cancer (PC) prognosis and diagnosis. Unfortunately, most circulating tumor cells (CTC) technologies, such as AdnaTest or Cellsearch®, critically rely on the epithelial cell adhesion molecule (EpCAM) marker, limiting the possibility of detecting cancer stem-like cells (CSCs) and mesenchymal-like cells (EMT-CTCs) that are present during PC progression. In this context, dielectrophoresis (DEP) is an epCAM independent, label-free enrichment system that separates rare cells simply on the basis of their specific electrical properties. As compared to other technologies, DEP may represent a superior technique in terms of running costs, cell yield and specificity. However, because of its higher complexity, it still requires further technical as well as clinical development. DEP can be improved by the use of microfluid, nanostructured materials and fluoro-imaging to increase its potential applications. In the context of cancer, the usefulness of DEP lies in its capacity to detect CTCs in the bloodstream in their epithelial, mesenchymal, or epithelial–mesenchymal phenotype forms, which should be taken into account when choosing CTC enrichment and analysis methods for PC prognosis and diagnosis.