Experimental animal and clinical studies have well established the association of prenatal exposure to diethylstilbestrol (DES) and the subsequent development of reproductive tract abnormalities, including poor reproductive outcome and neoplasia. Overwhelmingly, the focus has been on DES-induced epithelial lesions, particularly vaginal adenosis and adenocarcinoma; however, uterine smooth muscle cells are also recognized as cellular targets of DES. This descriptive report characterizes uterine leiomyomas that occur in outbred CD-1 mice following exposure to DES prenatally on days 9 to 16 of gestation or on neonatal days 1 to 5. These DES-induced uterine leiomyomas have typical histomorphologic, and some immunohistochemical characteristics of spontaneously occurring uterine smooth muscle tumors of B6C3F1 mice previously described in our laboratory, and they are also similar to uterine leiomyomas (fibroids) commonly observed in premenopausal women.