Endometriosis—endometrial tissue in an ectopic site outside the uterus—is one of the most common gynecologic disorders. The pathogenesis of this disease is controversial; the two major theories implicate either metaplasia or metastatic spread. In the ovary, endometriosis sometimes appears as endometriotic cysts. Occasionally, malignant tumors develop within these cysts, which therefore have been suggested to carry a neoplastic potential. We have investigated the clonal origin of five such ovarian cysts by a recombinant DNA X-chromosome inactivation technique. Three of the endometriotic cysts showed a monoclonal X-chromosome inactivation pattern, ie the cell populations of those cysts were each derived from one cell, whereas the remaining two cysts had polyclonal inactivation patterns. These findings suggest that endometriotic cysts can, in at least some cases, be regarded as neoplasic.