Endometriosis is a common chronic disease of women characterized by ectopic localization of the endometrial tissue in the peritoneal cavity. The pathogenesis of endometriosis closely resembles that of gynecological cancers in ways of menstruation- and ovulation-driven, wide intraperitoneal seeding, somatic hypermutation, and immune escape. While retrograde menstruation is regarded as the primary cause of endometriosis, the role of ovulation in the development of endometriosis has long been overlooked. We present the double engines, one checkpoint theory of the evolution of endometriosis. This new theory may lead to new concepts and strategies for preventing and treating this disease.