Circulating tumor cells (CTC) harvested in the blood of patients with esophageal squamous cell carcinoma (ESCC) are associated with certain clinical pathological parameters as well as patients’ prognosis and response to chemoradiation. They are the source of distant metastases and their mechanisms of pathogenesis is complex. In recent years, advance in technologies has allowed scientists to detect, enumerate, and isolate these cells for further analysis and monitor the diseases progression in patients with cancer. There are a few methods available for the identification of individual CTC and clusters of CTCs (circulating tumor microemboli). The most commonly used is detection by immunomagnetic method. Although all these methods have limitations, they are helpful for understanding the pathogenesis of CTCs with potential applications in clinical managements in patients with ESCC.