We report a case of a 37-year-old woman who had received five courses of gonadotropin-releasing hormone (GnRH) agonist (Decapeptyl) for presumed uterine leiomyomata associated with episodes of uterine bleeding. Submucous myoma (histologically proven) was partially removed on the first visit. After a period of significant reduction in the tumor size and cessation of uterine bleeding, the symptoms recurred along with rapid re-growth of the uterus. Total abdominal hysterectomy was performed and the pathologic evaluation revealed leiomyosarcoma with a high mitotic rate. This case and the literature review emphasize the problems encountered with the early diagnosis of uterine leiomyosarcoma during GnRH agonist therapy.