OBJECTIVE: To evaluate the usefulness of pre-operative serum CA-125 in the management of women diagnosed with uterine papillary serous carcinoma (UPSC). We hypothesized that elevated pre-operative levels of serum CA-125 correlate with higher disease stage and poorer prognosis. METHODS: Patients diagnosed with UPSC and managed in our institution were identified over a period of 10 years, 1995 to 2005. All required information were extracted from their records. The nonparametric test applied for comparison of data included Kruskal Wallis H-test and Man-Whitney U-test. The chi(2) test and Spearman correlation test were used to examine the association of serum CA-125 with different parameters. Receiver operator characteristic curves (ROC) were used to quantify marker performance. Recurrence and survival were analyzed using Kaplan-Meier method. Multivariate analyses were performed with a Cox proportional regression method. RESULTS: A total of 41 patients met the study criteria. Mean pre-operative serum CA-125 levels were significantly higher in patients with stage IV (1150+/-1297 U/mL), compared with stage III (181+/-232 U/mL; P<0.001), stage II (22+/-9; P<0.001), and stage I (14+/-1; P<0.001). CA-125 correlated strongly with stage (r=0.68, P<0.001). On the ROC, a cut-off of 35 IU/mL provided the best sensitivity and specificity (78% vs. 100% respectively) for extra-uterine disease. Disease free survival (DFS) and overall survival (OS) were longer in patients with CA-125<35 U/mL compared with CA-125>or=35 U/mL [median DFS not reached during study vs. 21.2 months (P=0.009), and median OS not reached during study vs. 25 months, (P=0.0001) respectively]. Multivariate regression model showed CA-125 as the only variable associated with survival (P=0.05). CONCLUSION: Pre-operative serum CA-125 levels correlate with stage of disease in patients with UPSC. This may be important for management planning, prognostication and counseling in these women.