Purpose: Monoclonal antibody (moAB) TKH-2 directed to the tumor-associated O-linked sialyl 2-6-α-N-acetylgalactosaminyl (sialyl Tn; STN) epitope was generated by immunization with ovine submaxillary mucin (Kjeldsen et al, Cancer Res 48:2214-2220, 1988). We investigated whether circulating serum levels of STN antigen might influence the prognosis of patients with ovarian cancer. Patients and Methods: Serum samples were obtained from 126 healthy nonpregnant women, 157 patients with benign gynecologic disease, and 89 patients with histologically proven epithelial ovarian cancer. Circulating serum STN-antigen concentrations (U/mL) were determined by a competitive radioimmunoassay kit (Otsuka Assay Laboratories, Tokushima, Japan) in a one- step procedure. Results: Serum antigen levels were elevated in 48.3% of the patients. The levels of STN antigen were significantly higher in the sera of patients with cancer when compared with levels in benign and healthy controls (P < .05). The 5-year survival rate for patients with STN-negative (serum STN levels < 50.0 U/mL) versus STN-positive (≥ 50 U/mL) tumors was 76.9% versus 10.8%, respectively (P < .05). The progression-free interval (PFI) at 5 years was 51.9% versus 5.4%, respectively (P < .05). The overall survival probability and PFI were worse in patients with STN-positive sera. Multivariate regression analysis revealed that stage, residual tumor size, positive STN, performance status, and histologic grade were the five important variables for predicting overall survival. Conclusion: We conclude that a positive STN-antigen level in sera is an independent predictor of poor prognosis in ovarian cancer.