The use of hormone replacement therapy (HRT) is currently a subject of debate because of the possibility of an increase in the incidence of breast cancer and difficulties associated with breast cancer detection. The objective of this study was to determine the influence of HRT on specificity and sensitivity in a breast cancer screening program. We found that although specificity was significantly lower in menopausal women who had ever used or were currently using HRT (93.3%) compared to HRT nonusers (94.8%) at the expense of a greater number of recalls (6.9% versus 5.6%), this difference seems to be clinically irrelevant. There were no significant differences with regard to the number of invasive procedures (2.5% in the HRT versus 2.1% in the control group). We conclude that the slight decrease in sensitivity of screening mammography in HRT users is not clinically significant in our setting, and in any case, false positives (recalled women) are diagnosed correctly with additional imaging studies without the need for invasive procedures. Most women given HRT are candidates to participate in population breast cancer screening campaigns.