Given the importance of tumor vasculature in tumor biology and as a target for treatment, there is an increasing need for biomarkers that reflect effects impacting tumor vasculature accurately. Circulating endothelial cells (CECs) increase in number as a result of vascular damage in cancer and several other diseases. CEC count constitutes a promising tool for monitoring disease activity with potential to assess prognosis and response to treatment. Here, we address the current state-of-the-art of CEC enumeration as a biomarker in clinical oncology. We focus on technical issues concerning CEC detection, review results from clinical studies and explore future potential applications.