OBJECTIVES: A major goal in the work-up of women with pelvic mass is to assess the risk of ovarian malignancy. Ovarian cancer has high mortality rates with 3000 deaths annually in Veneto Region of Italy. The utility of novel biomarkers, such as HE4 (Human Epididymis Protein 4), in diagnosis of ovarian cancer was investigated by a number of groups. These studies showed a high negative predictive value (NPV) of 97-99% indicating that almost all patients who tested negative were correctly diagnosed as having benign ovarian pathology. The objective of our study was to perform a budget impact analysis (BIA) and estimate the annual cost of the introduction of HE4 testing for differential diagnosis of women with pelvic mass for Regional Health Service in Veneto. METHODS: The study compares the cost of surgical intervention for pelvic mass versus the preoperative laboratory testing of HE4 biomarker for pelvic mass diagnosis. The incidence of pelvic masses, surgical interventions and costs for both procedures (surgery and HE4 test) were based on available statistics and reimbursement rates. RESULTS: AND CONCLUSIONS: If HE4 testing was performed in all potentially eligible women who present for preoperative pelvic mass evaluation in Veneto Region at a proposed cost of €35/patient, the total cost for Regional Health Service would be €1.130.075. Given the low false-positive rate for HE4 test, it can be hypothesised that cost from unnecessary procedures would be reduced. The BIA showed that if HE4 testing was performed in all potentially eligible women for preoperative pelvic mass evaluation (1st test) and as an additional 2nd follow up test in women who tested negative and avoided surgery, a conservative estimate of 10% reduction of surgical interventions would have a cost-neutral or even slightly positive impact on annual budget in Veneto, Italy.