The expression of sialyl-Tn antigen (STn) in normal, hyperplastic and neoplastic tissues of the uterine endometrium was examined by immunoperoxidase staining of formalin-fixed, paraffin-embedded samples using the monoclonal antibody TKH-2, directed toward the STn structure (NeuAc 2-6GalNac 1-O-serine or threonine). STn was expressed in 13 of 18 normal postovulatory endometria with an increasing staining intensity and incidence in the late secretory phase. It was consistently absent in 10 proliferative endometria. None of 5 cystic, 4 adenomatous or 12 atypical hyperplasias expressed STn, but areas of severe cytological atypia in 3 atypical hyperplasias showed faint expression. STn expression was detected in 36 of 43 adenocarcinomas. Although the extent of staining varied from a few to most of the cancer cells, general staining was observed throughout the cytoplasm of cancer cells with increased staining of the luminal surface and frequent positive staining of intraluminal mucin. Thus, it is clear that STn is selectively expressed in cancer cells and shows restricted expression in normal and hyperplastic endometrial tissues. STn may be an early marker of malignant transformation and has potential for use as a diagnostic aid in the surgical pathology of the uterine endometrium.