Circumstances that avert ovulation protect against serous (epithelial) ovarian cancer. The long-standing viewpoint was that serous ovarian cancer derives in situ from surface cells affected by ovulation; notwithstanding, it appears that precursor lesions present primarily within the ovarian end of the oviduct. Peritoneal dissemination of malignant cells characterizes late-stage disease. Serous ovarian cancer generally remains asymptomatic until tumor implants become established within the abdominal cavity. It is proposed that reactive oxygen molecules generated during ovulatory follicular rupture instigate base (oxoguanine) damages upon DNA of bystander ovarian surface and/or oviductal mucosal epithelial cells, that if gone unrepaired, can progress to mutagenesis, metaplasia/dysplasia, clonal expansion, and metastasis. Ovarian epithelial cells covering the apical surface of a follicle approaching ovulation undergo apoptotic death and are sloughed. The conventional scenario of serous carcinoma is that a defective extant cell circumjacent to the ovulatory stigma becomes incorporated into an inclusion cyst that ruptures and thereby seeds the peritoneum. It is conceivable that the oviductal mucosa interacting with the site of ovulation also is exposed to a genotoxin or could be colonized by a compromised epithelial cell captured from the ovarian surface (no ovarian pathology). Direct peritoneal seeding by a mutagenic cell shed from the ovarian surface or fimbria would explain circumstances where there is no clinical indication of ovarian or oviductal disease. Spread from a primary oviductal tumor to an ipsilateral ovary in route to widespread malignancy seems likely.