Retroperitoneal (pelvic) leiomyomas have recently come to be recognized as distinctive lesions. Retroperitoneal leiomyomas occur almost exclusively in women, and past studies on these invariably emphasized a striking similarity between their histological features, with those of uterine leiomyoma, whereas their origin remains unknown. In this study, we took notice of mesometrial smooth muscle, which has been little known either clinically or pathologically, as a possible origin of tumor. Anatomically, the mesometrial smooth muscle was an accumulation of thin bundles (approximately 1 mm in thickness) that ran parallel to the oviduct. It was connected broadly with the lateral wall of the uterine body and ended in the pelvic floor. The mesometrial smooth muscle was present just beneath the serosal surface of the anterior aspect of the mesometrium and continuously transited from the smooth muscle bundles of the outer layer of the uterine myometrium. The muscle cells were immunopositive for smooth muscle cell markers and estrogen/progesterone receptors. In all of the six female retroperitoneal leiomyomas examined, hormone receptor-positive nontumorous smooth muscle layers were present in the periphery of the tumors, seemingly representing the mesometrial smooth muscles. In conclusion, we believe most retroperitoneal (pelvic) leiomyomas in females arise from the mesometrial smooth muscle.