Tissue expression of VEGF-C correlates with lymph node involvement (LNI) in ESCC and serum VEGF-C (sVEGF-C) in a non-small cell lung cancer has been more accurate marker of LNI than chest CT. Despite LNI importance in ESCC, the usefulness of serum VEGF-C (sVEGF-C) as a disease and LNI marker in ESCC has not been investigated yet. We found elevated sVEGF-C in ESCC (17.40 vs. 10.57 ng/ml in controls, p<0.001). It proved to be a better ESCC marker than described elsewhere: CEA, CA19-9 and SCC-Ag, with: sensitivity--70%, specificity--81%, accuracy--83.7%. Analysis of sVEGF-C correlation with clinico-pathological cancer features revealed relation to LNI (N0: 15.77 vs. N1: 21.78 ng/ml, p=0.02), especially in advanced cancers. Serum VEGF-C as a marker of LNI was characterized by: sensitivity--76%, specificity--58%, accuracy--64.4%. No relation was observed between LNI and sVEGF-A or sVEGF-A/platelets (PLT). Because sVEGF-C was higher in N0 cancers (p<0.01), the tumor presence also up-regulates sVEGF-C. We found sVEGF-C correlation with PLT and WBC: R=0.36 and R=0.32 (p<0.01). Nevertheless, analysis of PLT and WBC dependence on cancer features implies that elevation of sVEGF-C in N1 cancers is not related to them.