Women with breast cancer are at a higher risk of developing vulvar and vaginal atrophy (VVA), a major component of the genitourinary syndrome of menopause, due to the combined estrogen-depleting effects of chemotherapy, adjuvant hormone therapy, and menopause. Ospemifene is approved to treat VVA in postmenopausal women with a history of breast cancer after completion of all breast cancer (including adjuvant) treatments. This article examines the background characteristics and outcomes in two postmenopausal women with a history of breast cancer who were treated with ospemifene for VVA. In the first case, a 78-year-old postmenopausal woman developed VVA while on aromatase inhibitor therapy for breast cancer. In the second case, a 54-year-old woman developed VVA many years after completing breast cancer therapy but not long after menopause. Both women had meaningful symptomatic improvement within 3 months of starting ospemifene treatment. Further improvement allowed each woman to resume sexual relations which had been a concern at presentation. Mammography and breast ultrasound imaging indicated no changes in breast tissue during treatment. Ospemifene is a useful therapeutic option for postmenopausal women with VVA and a history of breast cancer.