Background: Vulvar carcinoma is a rare gynecologic malignancy (incidence rate 3-5% of all female genital tract neoplasias) and mainly affects elderly women. Squamous cell carcinoma represent the vast majority of vulvar carcinomas (90-95%). TNM staging, deep of stromal invasion and presence of lymph node metastasis are the most important prognostic factors. Surgery is the standard treatment for primary vulvar carcinoma, followed by post operative radiotherapy when is neccesary. After primary treatment a high rate of patients develop recurrences, and a routine follow-up is necessary. Purpose: The ET-axis (Endothelin-1 and its receptors ETAR and ETBR) is overexpressed in various human tumors. We analyzed the ET-axis expression in vulva cancer, and its prognostic value. Methods: Samples were obtained from local excision and radical vulvectomy patients. ET-axis expression was investigated immunohistochemistry on tissue microarrays of 68 vulva cancer patients. Results: Elevated ET-1 expression of tumour cells is correlated high significantly to early stages pT1-T2 (P=0,004), and presence of metastasis (P=0,04). High staining levels ETBR within tumour tissue was related significantly to tumour progression (P=0,01), relapse-free survival (P=0,019), delayed metastasis (P=0,09 as a trend) and lymph node involvement (P=0,059 as a trend). A significant reduced overall survival could be shown concerning the low stages (pT1-2) (log rank P=0,036) and the patients without radiotherapy (log rank P=0,0539) as well as for the pM1 stage (log rank P= 0,0019). A significant reduced disease free survival could be shown concerning the low stages (pT1-T2) (long rank P=0,0206) with high ETBR expression. A correlation of both receptors was related significantly with tumour progression (P=0,022) and with local recurrence (P=0,005). Conclusions: These results suggest that, in addition to known histological risk factors and TNM classification criteria, measurement of ET-R expression with a simple immunohistochemical analysis might further help in predicting the prognosis of patients with vulva squamous cell carcinoma.