Ulipristal acetate is a selective progesterone receptor modulator that acts on progesterone receptors in uterine muscle and endometrium. It is effective in reducing the size of uterine leiomyomas (fibroids) and in managing associated menorrhagia. Although ulipristal acetate-associated pathologic changes have been previously documented in the endometrium, it is unclear what morphology can be expected in posttreatment fibroids. We herein report 2 cases in which patients underwent hysterectomy, after at least two 3-mo courses of ulipristal acetate. The fibroids demonstrated some pathologic changes that have previously been described associated with gonadotropin-releasing hormone agonist treatment and other progestogens. In addition, both cases demonstrated plexiform/"patchwork" fibrosis and vascular medial myxoid degeneration. Mitotic activity was absent; however, the presence of ischemic necrosis and mild nuclear atypia may mimic a more aggressive neoplasm in some areas. Awareness of these histopathologic patterns is important in the setting of ulipristal acetate treatment, to avoid over-diagnosis of "uncertain malignant potential" or malignant smooth muscle tumors.