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Objective: To examine the association between hormone replacement therapy (HRT) use and breast cancer incidence and to determine whether the association differs according to type of regimen. Method: Data were collected in Ontario from 404 incident cases and 403 age frequency-matched controls, between 1995 and 1996, using a self-administered questionnaire. Results: Multivariate analyses revealed an elevated odds ratio among long-term (≥ten years) HRT users (odds ratio (OR) = 1.80, 95% confidence interval (CI) 1.06–3.06). Risk among long-term estrogen–progestin users was substantially higher (OR = 3.48, 95% CI 1.00–12.11) than risk among long-term users of estrogen alone (OR = 1.74, 95% CI 0.93–3.24). Among both estrogen and estrogen–progestin users, positive associations were not observed for durations of use less than ten years. Conclusion: These data suggest that long-term use of HRT increases the risk of breast cancer and that estrogen–progestin therapy may be more detrimental than estrogen use alone.