Background and Objectives: Measurement of circulating endothelial cells (CECs) and progenitor cells (EPCs) has potential as a surrogate marker for monitoring anticancer treatment. This study evaluated the significance of CECs and EPCs in the blood of patients with head and neck squamous cell carcinoma. Methods: In a prospective trial fresh blood samples from 22 tumor patients and IS controls were tested rising multiparametric flow-cytometry. CECs were defined as CD31(+)/CD146(+) and CD45(-)/7AAD(-). EPCs were defined as CD133(+)/KDR+ and CD3(-)/CD19(-)/CD33(-)/7AAD(-). Results: Median levels (min/max) of CECs in the tumor group were 2 (015) at the time of diagnosis, 1 (0/5) 1 year after therapy and 2 (0/6) in the control-cohort. Median levels of EPCs were 5(1/41) before and 10(0/21) after treatment in the tumor group compared to 2(0/7) in the control cohort (P < 0.001 and P=0.03). CEC and EPC levels showed no apparent correlation with tumor size and response to radiotherapy after 18 months of observation, Conclusions: In this pilot Study CD133(+)/KDR+ EPCs were significantly elevated in head and neck tumor patients before and after therapy. Our results warrant further studies on the rise of EPCs as a surrogate marker for anticancer therapies in these patients.