A clear cell adenocarcinoma of the vaginal remnant in a diethylstilbestrol (DES)-exposed woman developed 20 years after anterior exenteration for a histologically similar stage II vaginal cancer. Arguments favoring a new primary cancer over a late recurrence are presented. This case probably represents the first report of a second primary vaginal clear cell cancer after DES exposure in utero. The implications of a second vaginal primary and the need for long-term surveillance in DES-exposed women are discussed.