A patient with adenoid cystic carcinoma was treated with mitoxantrone at a dose of 12 mg/m2 every 3 weeks. After the fifth dose, she developed amenorrhea accompanied by vasomotor instability (hot flashes). Subsequent serum gonadotropin and estradiol levels confirmed the postmenopausal state. The mechanism of mitoxantrone-associated amenorrhea is most likely due to direct toxic effects on the ovary, as is seen with other forms of chemotherapy. Ovarian dysfunction with mitoxantrone has not been previously reported. The important consequences of chemotherapy-induced ovarian failure are described. This toxic effect may be more frequently described as the drug becomes more widely available.