Ovarian cancer consists of many subtypes, serous carcinoma being the most common of them. In addition to the histopathological subtype, grading, clinical staging, and the amount of residual tumor, a great number of putative prognostic markers have been introduced. This study addresses in ovarian serous carcinoma the role of glycodelin, the major progesterone-regulated lipocalin protein of the reproductive axis with diverse actions in cell recognition and differentiation. Glycodelin expression was determined by immunohistochemistry of tissue microarrays in ovarian serous carcinomas from 460 patients, and the results were analyzed with respect to progesterone receptor subtype A (PRA) and progesterone receptor subtype B (PRB), clinical parameters, and survival. Glycodelin was localized to the cytoplasm of tumor cells, whereas vascular endothelium in tumor tissue was glycodelin-negative. Glycodelin expression was more frequent in well-differentiated (grade I, 79%) than in poorly differentiated carcinomas (grade III, 51%; P < 0.0001), and it was also more frequent in early-stage compared with advanced-stage carcinomas (P = 0.002). Nuclear PRA and PRB were often coexpressed with cytoplasmic glycodelin. Although this was not consistent in all tumors, there was a positive correlation between the presence of glycodelin and PRs in the tumor (P < 0.02), but not between the presence of, or the absence of, glycodelin in tumor and the CA-125 serum concentration. Although in multivariate analysis glycodelin was not an independent variable, the patients with glycodelin-expressing tumors showed a higher 5-year overall survival compared with those with glycodelin-negative tumors (55 versus 39%; P < 0.0001; hazard ratio in univariate analysis, 0.57; confidence interval, 0.44-0.74). This difference was notable in patients with grade I tumors and stage III disease. In the latter group, the 10-year survival probability of patients with glycodelin-positive tumors was more than twice as high as that in women with glycodelin-negative tumors. This was also found within well-defined clinical categories, e.g., stage III/grade II and stage III/grade III carcinomas, in which patients with glycodelin-positive tumors carried significantly better 10-year overall survival compared with those with glycodelin-negative tumors. It is concluded that, in ovarian serous carcinoma, glycodelin expression portends better prognosis, probably because of its differentiation-related disposition.