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Ovarian cancer is the ninth most common cancer diagnosed in Australian women, but the fifth most common cause of cancer related death. One pathway involved in ovarian cancer is Wnt, a key developmental pathway which is often dysregulated in human cancer and is thought to play a role in epithelial to mesenchymal transition (EMT) and metastasis.Expression of the Wnt ligand Wnt-5a was investigated in a large cohort of 721 benign, borderline and ovarian cancer patients. Wnt-5a expression was significantly higher in ovarian cancer patients compared to benign and borderline patients (p < 0.0001). Patients with high Wnt-5a expression had a shorter relapse free and disease specific survival compared to patients with low or absent Wnt-5a (p < 0.05). There was no difference in Wnt-5a expression amongst the subtypes of ovarian cancer (p > 0.05). Wnt-5a expression wasalso correlated with clinico-pathological parameters of ovarian cancer, namely the present tumour marker CA-125 (p < 0.05), patient age (p < 0.0001), ascites (p < 0.0001), residual disease (p < 0.0001) and advanced FIGO Stage (p < 0.0001). In addition, there was a significant negative correlation between Wnt-5a expression and SFRP4 an antagonist of the Wnt signalling pathway (p < 0.0001). This data shows that Wnt-5a is associated with more aggressive disease and is a predictor of poor prognosis in ovarian cancer patients.In vitro studies were conducted to investigate the functional effect of Wnt-5a modulation in the normal epithelial ovarian cell line HOSE 6.3 by using a recombinant protein form of Wnt-5a. Wnt-5a expression significantly decreased the expression of β–catenin dependent Wnt signalling targets CCDN1 (p < 0.01), Axin2 (p < 0.01) and MYC (p < 0.001), and significantly increased the expression of β–catenin independent Wnt signalling targets NFAT (p < 0.01), JNK (p < 0.01), PRKCA (p < 0.01) and MMP13 (p < 0.001). Wnt-5a expression in HOSE 6.3 induced EMT since CDH1 (E-cadherin) express