Objective: Primary peritoneal high-grade serous carcinoma is thought to arise from the peritoneum, but recent data suggest that the fallopian tube may be an occult source of many of these tumors. This study was performed to evaluate this hypothesis in an unselected series of cases. Methods: Fallopian tubes from 51 consecutive cases meeting the GOG criteria for primary peritoneal high-grade serous carcinoma, FIGO stages II-IV, were analyzed. Results: Serous tubal intraepithelial carcinoma (STIC) was identified in 19 patients (37%). When the fimbriae were examined, STIC was identified in 46%, and when all tubal tissue was examined, 56%. STIC was confined to the fimbriae in 53%, involved fimbriae and nonfimbrial mucosa in 20%, and was confined to nonfimbrial mucosa in 20%. Patients with STIC were significantly older than those without STIC (75 years vs. 67 years, respectively; p = 0.007). Patients with STIC were significantly more likely to have FIGO stage IV disease as compared to those without STIC (42% vs. 12.5%, respectively; p = 0.037). Conclusions: At least half the cases of primary peritoneal high-grade serous carcinoma are associated with intraepithelial carcinoma of the fallopian tube, usually involving the fimbriae. These findings support the view that, like "primary ovarian carcinoma," what has been traditionally classified as "primary peritoneal carcinoma" is probably derived from occult high-grade serous carcinoma in the fallopian tube. These findings have important implications for ultrasound screening trials for ovarian cancer which are based on the assumption that an enlarged ovary is a very early manifestation of disease. © 2010 Elsevier Inc. All rights reserved.