Background: Breast cancer incidence rate in Belgian women was as high as 152.7 for 100 000 in 2003 (adjusted on European population). We made an estimation of the contribution of hormone replacement therapy (HRT) on breast cancer incidence from 1999 to 2005 in women aged 50–69 years in Flanders. Methods: Breast cancer data were extracted from the Belgium Cancer Registry. Drug consumption was computed from drug sales data. The fraction of breast cancers attributable to HRT was calculated by year, using the relative risks of the Million Women Study in the UK. Results: The proportion of women aged 50–69 years using HRT in Flanders increased since 1992, peaked at 20% in 2001, then decreased to 8% in 2008. The incidence of breast cancer in 100 000 women aged 50–69 years in Flanders increased from 332.8 in 1999 to 407.9 in 2003, then decreased to 366.1 in 2005; the variations were mostly noticeable for tumors <20 mm in size. The fraction of breast cancers attributed to HRT peaked at 11% in 2001 and decreased afterward. Conclusion: The high level of breast cancer observed in the years 2001–2003 in Flanders can be partly attributed to the use of HRT. Since participation to mammography screening of Flemish women aged 50–69 years was still on the rise in 2003 and never exceeds 62%, the decrease in breast cancer incidence was likely to be due to the decrease in HRT use and not to screening saturation.