The oncogene-inducible secreted T1-S glycoprotein is overexpressed in invasive breast carcinomas in mice. As yet, nothing is known about the expression of T1-S in spontaneously occurring human cancers. A report follows on the overexpression of T1-S mRNA in 67% of primary invasive lymph node-negative breast carcinomas (31 of 46 patients) as determined by quantitative reverse transcriptase polymerase chain reaction. Overexpression of T1-S mRNA was independent of the tumor size, the histologic tumor type, and the estrogen-and progesterone-receptor status but was associated with high to moderate differentiation of the tumors (G , G2). T1-S mRNA levels were low to nondetectable in resting normal mammary tissue and benign fibrocystic disease of the breast. Immunohistochemistry confirmed a low to moderate T1 immunoreactivity in epithelial cells of resting mammary tissue and benign fibrocystic disease and highly variable levels of T1 immunoreactivity in breast carcinoma cells. Kaplan-Meier analysis of disease-free survival during a median observation period of 61 months revealed a trend toward a reduced relapse rate and an extended relapse-free survival period for T1-S mRNA--overexpressing breast carcinomas. It is concluded that overexpression of T1-S receptor in lymph node-negative breast cancer may be a potential indicator for tumors with a low metastatic potential.