Previous studies have reported that breast cancer patients who used estrogen replacement therapy (ERT) have more favorable tumor characteristics and decreased mortality compared with nonusers. However, these findings may be due partly to increased medical surveillance in ERT users and detection of early stage tumors. Postmenopausal women with biopsy-proven breast cancer (n = 108) were identified based on their participation in screening mammography. Based on self-administered questionnaires completed at the time of mammography, 29 of these were users of ERT. Tumor characteristics (histology size, nodal status, and estrogen receptor content) of ERT users were compared with those of nonusers. After adjusting for potentially confounding variables, the odds ratios (OR) describing the relationship between ERT use and the risk of invasive histopathology (OR = 1.35, 95% CI = 0.48, 3.75), positive nodes (OR = 2.43, 95% CI = 0.59, 10.10), size greater than or equal to 2.0 cm (OR = 2.34, CI = 0.66, 8.27), or negative estrogen receptor status (OR = 1.08, 95% CI = 0.18, 9.38) were >1, although none reached statistical significance. When the subjects were separated into two prognostic groups based on the presence or absence of adverse prognostic indices, ERT users had a statistically significantly increased risk of being in the poor prognostic group (tumor size greater than or equal to 2.0 cm or positive nodes or negative estrogen receptor content) (OR = 4.48, 95% CI = 1.10, 18.30). The risk was highest in current users (OR = 6.28, 95% CI = 1.16, 34.00), users for 5 or more years (OR = 7.77, 95% CI = 1.09, 55.60), and users of nonconjugated estrogen (OR = 9.63, 95% CI = 1.18, 78.60). Although our sample size is small and we do not currently have information on longterm outcomes, the findings from this screening population suggest that ERT may have an adverse effect on important breast cancer prognostic indices.