The influence of body size on postmenopausal breast cancer risk was investigated among five racial/ethnic groups in the Multiethnic Cohort. Participants were 45–75 years old at recruitment (1993–1996), living in Hawaii and California. Of the 82,971 White, African American, Native Hawaiian, Japanese and Latina women included in this analysis, 3,030 were diagnosed with invasive breast cancer. Body mass index (BMI), height, weight and adulthood weight gain were associated with a significantly higher risk and, with the exception of height, were found to vary across ethnic groups. Native Hawaiians and Japanese with a BMI ≥30.0 compared to 20.0–24.9 kg/m2 had the highest risk (hazard ratio = 1.82, 95% confidence interval: 1.31, 2.54, p-trend = 0.001, and hazard ratio = 1.59, 95% confidence interval: 1.24, 2.05, p-trend < 0.0001, respectively). Current hormone replacement therapy use modified the impact of a high BMI, as non- and former users had a significantly higher risk compared to current users. BMI also had a more pronounced risk for advanced tumors compared to localized tumors. When both BMI and adult weight gain were analyzed simultaneously, adult weight gain, rather than BMI, was a significant risk factor overall. These findings emphasize the significance of maintaining a healthy weight throughout adulthood for the prevention of postmenopausal breast cancer.