This proof-of-concept study, comparing the combination of urine CA125 and HE4 with serum CA125, is the first to be reported, and an important preliminary step in biomarker development, demonstrating the ability of urine CA125 and HE4 to detect ovarian cancer cases from symptomatic controls, the majority of whom had early-stage disease. This evidence concerns the gene WFDC2 and ovarian cancer.