The objective of this prospective study was to evaluate CA-125 and a 7-marker panel as predictors of incomplete primary cytoreduction in patients with stage III/IV ovarian cancer (OC). From September 2004 to January 2008, serum from 201 patients referred to surgery for a pelvic tumor was analyzed for CA-125. In addition, serum was analyzed for 7 biomarkers using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. These biomarkers were combined into a single-valued ovarian-cancer-risk index (OvaRI). CA-125 and OvaRI were evaluated as predictors of cytoreduction in 75 stage III/IV patients using receiver operating characteristic curves. Complete primary cytoreduction (no macroscopic residual disease) was achieved in 31% (23/75) of the patients. The area under the receiver operating characteristic curve was 0.66 for CA-125 and 0.75 for OvaRI. The sensitivity and specificity of CA-125 for predicting incomplete cytoreduction were 71% (37/52) and 57% (13/23), respectively (P = 0.04). The sensitivity and specificity of OvaRI for predicting incomplete cytoreduction were 73% (38/52) and 70% (16/23), respectively (P = 0.001). In conclusion, CA-125 and an index of 7 biomarkers were found to be predictors of cytoreduction. However, future studies of biomarkers are anticipated to promote early diagnosis and provide prognostic information to guide treatment of OC patients. In addition, new biomarkers might also play a role in predicting outcome from primary surgery in OC patients.