Circulating tumor cells (CTCs) are rare cells shed from primary and metastatic cancers, making their isolation and characterization challenging. CTCs hold significant potential for understanding metastasis and serving as biomarkers for noninvasive monitoring of tumor evolution during treatment and disease progression. Advances in CTC isolation technologies, such as nucleic acid-based detection, physical property-based separation, and antibody-based capture, have improved the yield and purity of CTC populations. However, the low frequency of CTCs and the presence of contaminating leukocytes remain major challenges. The identification of molecular aberrations, signaling pathways, and cellular properties in CTCs can provide insights into tumor biology and treatment responses. CTC clusters, which have been observed in some patients, may also play a role in metastasis. Future perspectives include the development of more sensitive and reliable CTC isolation methods, enabling broader applications in early cancer detection and personalized therapy.Circulating tumor cells (CTCs) are rare cells shed from primary and metastatic cancers, making their isolation and characterization challenging. CTCs hold significant potential for understanding metastasis and serving as biomarkers for noninvasive monitoring of tumor evolution during treatment and disease progression. Advances in CTC isolation technologies, such as nucleic acid-based detection, physical property-based separation, and antibody-based capture, have improved the yield and purity of CTC populations. However, the low frequency of CTCs and the presence of contaminating leukocytes remain major challenges. The identification of molecular aberrations, signaling pathways, and cellular properties in CTCs can provide insights into tumor biology and treatment responses. CTC clusters, which have been observed in some patients, may also play a role in metastasis. Future perspectives include the development of more sensitive and reliable CTC isolation methods, enabling broader applications in early cancer detection and personalized therapy.