After the first description of epidermoid carcinoma of the vagina by Jean Cruveilhier in 1827, 1 Cruveilhier J Varices des veines du ligament rond, simulant une hernie inquinale. Anomalie remarquable dans la disposition général du péritoine. Cancer ulcéré de la paroi antérieure du vagin et du bas-fond de la vessie. Col utérin, proéminent, etc. Bull Soc Anat Paris. 1827; 2: 199-205 Google Scholar this condition remained relatively uncommon as compared with carcinoma of the cervix, which occurs about 20 times more frequently. 2 Cruveilhier J Volumes 1 and 2: anatomie pathologique du corps humain. in: JB Baílliere, Paris1829: 1842 Google Scholar , 3 Ricci JV One hundred years of gynaecology, 1800-1900. in: Blakiston, Philadelphia1945: 448 Google Scholar Even more rare is adenocarcinoma or clear cell type. In 1970, Arthur L. Herbst and Robert E. Scully 4 Herbst AL Scully RE Adenocarcinoma of the vagina in adolescence: a report of 7 cases including 6 clear cell carcinomas (so-called mesonephromas). Cancer. 1970; 25: 745-757 Crossref PubMed Scopus (368) Google Scholar reported 7 cases of clear cell adenocarcinoma in young women between the ages of 15 and 22 years, which were seen at a single hospital in Boston. The following year, Herbst, together with Ulfelder and Poskanzer, 5 Herbst AL Ulfelder H Poskanzer DC Adenocarcinoma of the vagina: association of maternal stilbestrol therapy with tumor appearance in young women. N Engl J Med. 1971; 284: 878-881 Crossref PubMed Scopus (2027) Google Scholar reported on 8 patients with this condition, the mothers of 7 of whom were treated with diethylstilbestrol (DES) during the first trimester of pregnancy. Table I from that article summarized the chronologic details of each patient, together with therapy and results, and demonstrated the clustering of patients in regard to time of birth and occurrence of tumor. Table II presents a comparison of pertinent data on the patients with those of the matched control subjects. Alerted to this association, Herbst and Scully established a Registry for Research on Hormonal Transplacental Carcinogenesis. Subsequent studies confirmed that all but a few cases showed an association between the vaginal adenocarcinoma and DES exposure. 6 Ulfelder H Stilbestrol, adenosis, and adenocarcinoma. Am J Obstet Gynecol. 1973; 117: 794-798 Abstract Full Text PDF PubMed Scopus (12) Google Scholar During the late 1940s, 1950s, and later, DES had been used therapeutically in early pregnancy in the belief that it would decrease complications such as toxemia of pregnancy and bleeding and help to reduce the incidence of premature births and neonatal deaths. 7 Smith OW Diethylstilbestrol in the prevention and treatment of complications of pregnancy. Am J Obstet Gynecol. 1948; 56: 821-834 Abstract Full Text PDF PubMed Scopus (171) Google Scholar , 8 Smith OW Smith GVS Use of diethylstilbestrol to prevent fetal loss from complications of late pregnancy. N Engl J Med. 1949; 241: 562-568 Crossref PubMed Scopus (26) Google Scholar , 9 Smith OW Smith GVS Hurwitz D Increased excretion of pregnanediol in pregnancy from diethylstilbestrol with special reference to the prevention of late pregnancy accidents. Am J Obstet Gynecol. 1946; 51: 411-415 Abstract Full Text PDF PubMed Scopus (57) Google Scholar Subsequent reports by Herbst and his colleagues, and others, established the strong association between DES and vaginal clear cell adenocarcinoma. 10 Barnes AB Colton T Gunderson J Noller KL Titley BC Strama T et al. Fertility and outcome of pregnancy in women exposed in utero to diethylstilbestrol. N Engl J Med. 1980; 302: 609-613 Crossref PubMed Scopus (111) Google Scholar , 11 Herbst AL Cole P Colton T Robboy SJ Scully RE Age-incidence and risk of diethylstilbestrol-related clear cell adenocarcinoma of the vagina and cervix. Am J Obstet Gynecol. 1977; 128: 43-50 Abstract Full Text PDF PubMed Scopus (168) Google Scholar , 12 Herbst AL Poskanzer DC Robboy SJ Friedlander L Scully RE Prenatal exposure to stilbestrol. A prospective comparison of exposed female offspring with unexposed controls. N Engl J Med. 1975; 292: 334-339 Crossref PubMed Scopus (190) Google Scholar , 13 Kaufman R Adam E Binder GL Gerthoffer E Upper genital tract changes and pregnancy outcome in offspring exposed in utero to diethylstilbestrol. Am J Obstet Gynecol. 1980; 137: 299-308 Abstract Full Text PDF PubMed Scopus (134) Google Scholar , 14 Wilcox AJ Baird DD Weinberg CR Hornsby PP Herbst AL Fertility in men exposed prenatally to diethylstilbestrol. N Engl J Med. 1995; 332: 1411-1416 Crossref PubMed Scopus (212) Google Scholar This was the first instance of prenatal drug exposure–induced cancer in humans and helped to alert physicians and others to the potential adverse consequences of the use of medications during pregnancy.