UN1 antigen (Ag), a 100-120 kDa sialoglycoprotein, was initially identified on immature thymocytes (CD3(dim)), a small subpopulation of CD4(+) peripheral blood T-lymphocytes, on leukemic T-cell lines and in fetal thymus. Biochemical analysis of the Ag has identified molecular features that are characteristic of cell-membrane-associated mucin-like glycoproteins. To investigate the biological role and the potential usefulness of the Ag, we have more extensively studied the pattern of UN1 Ag expression in a panel of fetal tissues, at different gestational ages, and on adult normal and tumor specimens. In the fetal samples examined by immunohistochemistry, including intestine, liver, lung and adrenal gland, we found that UN1 Ag is widely expressed during early stages of fetal development and down-regulated during ontogenesis. Very poor or not detectable expression of UN1 Ag was found at late gestational age. Immunohistochemical, Western blot and flow cytometric analysis of a panel of normal adult tissues and benign lesions failed to find Ag expression, whereas UN1 Ag was highly detectable in a variety of cancer specimens from breast, lung, gastrointestinal, gynaecological malignancies and melanomas. Based on these data UN1 Ag, for the wide expression on fetal tissues, the down-regulation during ontogeny and the re-expression in cancer cells, may be considered a novel oncofetal Ag of interest for biological investigation and clinical applications.