Circulating tumor cells (CTCs) are a valuable biomarker for the diagnosis, prognosis, and therapeutic management of gastrointestinal (GI) cancers. A major challenge in GI cancer treatment is the high rate of metastasis, which significantly contributes to cancer-related mortality. CTCs are crucial in the metastatic cascade, serving as indicators of tumor progression. Therefore, the detection and molecular characterization of CTCs have prognostic potential for identifying early-stage GI cancers and assessing metastatic probability, enabling timely treatment. Moreover, CTC analysis offers a minimally invasive method for real-time monitoring of tumors.Clinicians can adjust therapeutic strategies accordingly by tracking changes in CTC count and molecular profile. Despite this promising application, no standardized protocol for CTC isolation in GI tract cancers has been established, which poses a barrier to routine clinical use. This review explores the current CTC detection methodologies, their clinical relevance in GI cancer management, and the potential integration of CTC analysis into personalized medicine. We also discuss the challenges and future directions in CTC research, focusing on clinical validation and the development of standardized procedures to fully realize the utility of CTC count for improving patient care.