The identification of glypican-3 (GPC3) expression in malignant neoplasms is potentially of interest because GPC3 might represent a therapeutic target. Tissue microarrays containing tissue cylinders from 308 patients with ovarian carcinomas were used for an immunohistochemical study. There were 255 serous, 38 endometrioid, and 15 clear-cell carcinomas included. From 76 patients, paired tissue samples of primary serous ovarian carcinomas and their corresponding recurrences after platinum-based chemotherapy were available. Glypican-3 was expressed in a total of 17.9% of ovarian carcinomas and was strongly associated with the clear-cell histotype (P = 0.0001). Glypican-3 expression was not associated with tumor stage. Positive staining for GPC3 was also observed in a significant fraction of recurrent carcinomas but was not particularly associated with chemoresponse. In conclusion, our data show that GPC3 is observed in a significant fraction of primary and corresponding recurrent ovarian carcinomas. Glypican-3 may therefore represent a potential target for (second-line) therapy in ovarian cancer.