Hormone replacement therapy (HRT) has been considered one of the main risk factors for breast cancer. Studies demonstrating the relationship between HRT and breast cancer incidence were conducted in Western countries and the target populations were mainly Caucasians. Since the Women's Health Initiatives demonstrated that HRT increased the risk of breast cancer with statistical significance, the number of HRT users in the United States has dramatically decreased. A recent case-control study has investigated the relationship between HRT and breast cancer in Japan, and here we review the results of this study to compare any discrepancy in breast cancer risk between Japanese and Western populations. For this case-control study, at seven institutions, women between the ages of 45 through 69 years, with histologically confirmed breast cancer, were selected as the case group. An age-adjusted control group was selected, using hospital-based data, including records of those screened for lung, gastrointestinal, and gynecological cancer. Questionnaires were administered, and items questioned included various factors related to the incidence of breast cancer: age at diagnosis, body mass index (BMI), smoking habit, age at menopause, birth history, number of births, number of children, history of breast feeding, familial background, and menopausal status. In total, 6183 samples (98.4% of the estimated samples) were put into the database. Data from 276 samples were excluded due to ineligibility. Finally, 5861 samples (3434 cases and 2427 controls) were analyzed. In 3316 cases, 164 (5.0%) patients received hormone-replacement therapy (HRT); on the other hand, 253 (10.7%) of 2355 controls received HRT. The odds ratio was 0.432 (95% confidence intervals [CI], 0.352-0.53), and there was a significantly negative correlation between HRT use and breast cancer. The risk factors in Japanese women showed similar profiles to those in women in Western countries. However, we did find some different profiles of breast cancer risk in the Japanese women. Changing of lifestyle may increase breast cancer risk in Japan.