Serum C-reactive protein (CRP), a sensitive marker of systemic inflammation, has been reported to be associated with the risk of a number of cancers including breast cancer. However, the results are inconsistent. To investigate the association between serum CRP levels and early breast cancer, we conducted a hospital-based case-control study among 506 newly diagnosed breast cancer patients and 506 controls with benign breast diseases matched by age and menopausal status. Odds ratios (ORs) were computed with unconditional logistic regression models, adjusted for major confounding factors. Relative to women with the lowest quartile of CRP level, women with the highest quartile had 1.65-fold increased breast cancer risk (OR: 1.65, 95% CI: 1.12-2.42) in a significant dose-response manner (p(trend) = .011). Stratification analysis revealed a positive association only for overweight postmenopausal women (highest CRP quartile versus lowest CRP quartile: OR: 2.78, 95% CI: 1.18-6.6). Multinominal logistic regression analysis showed that only hormonal receptor (HR) positive and human epidemiological receptor 2 (HER2) negative breast cancers had elevated serum CRP levels. We observed that elevated serum CRP levels are positively associated with early breast cancer, predominantly among overweight and postmenopausal women. This study provided epidemiological evidence that chronic inflammation might mediate the association between obesity and postmenopausal breast cancer. Although a positive association between serum CRP and HR positive/HER2 negative breast cancer is intriguing, further epidemiological studies are needed to confirm such findings.