CA 125 and cancer-associated serum antigen (CASA) were measured prior to second-look laparotomy (SLL) to investigate their predictive and prognostic values in 93 patients treated for epithelial ovarian cancer FIGO stage II, III, or IV. Residual tumor was diagnosed at the SLL in 58 patients (62%). The optimal cutoff level was 15 U/ml for CA 125 and 8 U/ml for CASA. Using these levels, the sensitivity for detection of residual tumor was 40% for CA 125 and 22% for CASA. The combined use of the markers resulted in a sensitivity of 47% (diagnostic gain 6.9%; 95% confidence interval (CI), 0.14-13.44%). Microscopic tumor volumes were equally diagnosed by CASA and CA 125. The independent prognostic value of CA 125 (RR = 2.6; 95% CI, 2.0-3.2) and CASA (RR = 2.2; CI, 1.5-2.9) was established by means of Cox regression analysis of the covariation between survival, age, FIGO stage, histopathology, tumor grade, and bulk of residual tumor at the primary operation and CA 125 and CASA before the SLL. In conclusion, we found that CASA could supplement CA 125 measurement prior to SLL and reduce the number of SLLs. Furthermore, CASA had an independent prognostic value for survival which may be used together with other information in the planning of further treatment of the individual patient.