Abstract :Introduction: Nodal metastasis is a main prognostic factor in vulvar cancer. Increased vascular endothelial growth factor C (VEGF-C) expression has been associated with lymph node metastasis and poor prognosis in many cancers. The aim of this retrospective study was to investigate VEGF-C expression pattern in the invasive edge of vulvar cancer and in sentinel lymph node metastasis, and its association with the stage and prognosis. Methods: Tumor and sentinel lymph node samples from 44 patients were evaluated with immunohistochemistry, and the results were linked with the clinicopathological data. Results: Sixty-seven percent of primary tumors and 76% of sentinel lymph node metastases expressed VEFG-C. Positive VEGF-C expression of the primary tumor did not predict surgical Stage or sentinel lymph node involvement. The risk of relapse was not significantly higher with VEGF-C expressing tumors than with VEGF-C negative tumors (RR 2.55, 95% CI 0.66-9.90, p = 0.18). The risk of groin recurrence was significantly lower with VEGF-C positive than negative tumors (RR 0.36, 95% CI 0.16-0.79, p = 0.01). Survival was similar in both groups. No non-sentinel lymph node metastases were found in case of negative VEGF-C expression in the sentinel lymph node metastasis, whereas with positive VEGF-C expression they were found in 5/13 (38%) of cases. Conclusions: Tumoral VEGF-C expression was not associated with higher surgical Stage or poorer prognosis in vulvar cancer. However, absence of its expression in sentinel lymph node metastasis might indicate a low risk for non-sentinel lymph node metastases.