Serous ovarian, Fallopian tube, and peritoneal adenocarcinomas are remarkably similar, both in their morphology, as well as in their clinical behavior. Despite extensive clinical and fundamental research, controversy still exists on the origin of serous female adnexal tumors. Difficulties in identification of site of origin at late stage the of disease at detection, when ovary, Fallopian tube, and the abdominal cavity are usually all involved, in addition to their macroscopic and microscopic resemblance, are major causes of this debate. In 3 hypotheses, 3 possible tissues of origin are proposed: the ovarian surface epithelium, the Fallopian tube epithelium, and the secondary Müllerian system.

We searched for all peer-reviewed articles and reviews that examined “serous ovarian carcinoma,” “Fallopian tube carcinoma,” “Müllerian system,” “ovarian surface epithelium,” “tubal epithelium,” and “peritoneal.” We included only articles that could give information on the origin of serous carcinomas. Additional articles were added by examining references of overview articles in relevant fields.

Discussed are the experimental data underlying these hypotheses.

An attempt is made to integrate the 3 hypotheses into a comprehensive model of serous intraperitoneal adenocarcinogenesis. It can be concluded that the Fallopian tubes play a major role in the development of female serous cancer.