Late-stage ovarian carcinoma is almost universally fatal. BRCA mutations are associated with an improved outcome and enhanced sensitivity to platinum chemotherapy, yet recurrence and platinum resistance remain a major problem and highly effective regimens following platinum failure do not yet exist. Here we report a remarkable case of cure following platinum-resistant stage III ovarian carcinoma in a woman with a BRCA2 mutation. The patient was subsequently treated with oral melphalan therapy and has not recurred in over 25 years. Melphalan is a bifunctional alkylator that creates inter- and intra-strand DNA cross-links. In a pharmaceutical screen, melphalan was shown to be selectively toxic to BRCA2-deficient breast cancer cell lines and produced a longer relapse-free survival in mice than did cisplatin or olaparib. There is increasing evidence to consider BRCA mutation status when selecting chemotherapy regimens, and melphalan treatment for BRCA-related ovarian cancer merits further investigation. Focusing attention on long-term survivors may provide new mechanistic insights into the biology of chemo-responsiveness.