The aim of this study is to determine immunohistochemical markers with prognostic significance for disease-specific survival in patients with squamous cell cancer of the vulva. The study material consisted of slides and paraffin blocks of 50 vulvectomy specimens. A tissue microarray was constructed and stained with 16 antibodies. The impact of lymph node metastases, size of tumor, vascular space involvement, and the marker expression on disease-specific survival was calculated. In univariate analysis lymph node metastases, tumor size more than 4 cm, vascular space involvement, strong cyclooxygenase 2 expression, and absent Caspase 3 expression were significantly associated with disease-specific survival. In a multivariate analysis, poor disease-specific survival is independently associated with absent Caspase 3 expression (hazard ratio, 0.2; 95% confidence interval, 0.04-0.97; P = 0.045). Five-year survival was 86% in patients with tumors positive for Caspase 3 (n = 20) and drops to 64% in patients with Caspase 3-negative tumors (n = 30). In this test set, cyclooxygenase 2 and Caspase 3 seem to be immunohistochemical markers with prognostic significance for vulva cancer. The results have to be validated.