Diethylstilbestrol is known to be a human carcinogen based on sufficient evidence of carcinogenicity of in humans. Diethylstilbestrol taken during pregnancy has been shown to increase the incidence of clear cell adenocarcinomas of the vagina or cervix and vaginal adenosis in daughters exposed in utero. The evidence for an association with other human cancers is either limited (endometrium) or inadequate (breast, ovary).

An IARC Working Group reported that there is sufficient evidence of carcinogenicity of diethylstilbestrol in experimental animals. When administered orally (by gavage or in the diet), diethylstilbestrol induced mammary carcinomas and adenocarcinomas in mice of both sexes. One study reported adenocarcinomas of the cervix, endometrium, and uterine horns in female mice given diethylstilbestrol in the diet. Male and female rats fed diets containing diethylstilbestrol developed pituitary tumors and male rats developed mammary tumors (mostly fibroadenomas). Subcutaneous injection resulted in increased incidences of leukemia and breast tumors in male mice; breast tumors in male mice suckled by diethylstilbestrol-injected females; ovarian cystadenomas in adult female mice; and cancers of the cervix and vagina in newborn female mice. Castrated newborn male rats developed invasive squamous cell carcinomas of the coagulatory gland or ejaculatory duct when injected subcutaneously.

Diethylstilbestrol by subcutaneous injection induced increased incidences of renal carcinomas in male hamsters and ovarian papillary carcinomas in female dogs. Subcutaneous implants of diethylstilbestrolcontaining pellets induced interstitial cell tumors of the testis, mammary tumors, or lymphoid tumors in male mice and mammary carcinomas and lymphoid tumors in female mice. Subcutaneous implants in rats induced mammary carcinomas and urinary bladder carcinomas in conjunction with calculi in both sexes. Subcutaneous implants induced malignant adenomatous renal tumors, with many metastases, in male hamsters and malignant uterine mesotheliomas in female squirrel monkeys. Prenatal exposure to diethylstilbestrol induced adenocarcinomas of the uterine endometrium, epidermoid tumors of the cervix and vagina, and cystadenomas and granulosa cell tumors of the ovary in female mice and lung papillary adenomas in mice of both sexes. Prenatal exposure to diethylstilbestrol induced high incidences of metaplastic, dysplastic, and neoplastic lesions of the genital tract, including cervical polyps; and squamous cell papillomas of the cervix and vagina; in female hamsters and granulomas in the epididymis and testis and epididymal cystic formations in male hamsters.