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Current developments in the treatment of genitourinary tumors underline the unmet clinical need for biomarkers to improve decision-making in a challenging clinical setting. The detection of circulating tumor cells (CTCs) has become one of the most exciting and important new approaches to identifying biomarkers at different stages of disease in a non-invasive way. Potential applications of CTCs include monitoring treatment efficacy and early detection of progression, selecting tailored therapies, as well as saving treatment costs. However, despite the promising implementation of CTCs in a clinical scenario, the isolation and characterization of these cells for molecular studies remain expensive with contemporary platforms, and significant technical challenges still need to be overcome. This updated, critical review focuses on the state of CTCs in patients with genitourinary tumor with focus on prostate cancer, discussing technical issues, main clinical results and hypothesizing potential future perspectives in clinical scenarios.