Serum amyloid A (SAA) is an acute-phase protein and also an adipokine, which has been associated with the development and prognosis of breast cancer. In the present study, we investigated the association between obesity and SAA in postmenopausal women with breast cancer and its relationship with clinicopathologic characteristics of tumors. Patients were grouped as nonobese or overweight/obese based on body mass index (BMI) plus waist circumference measurement. Serum SAA concentrations were determined by high-sensitivity micro-latex agglutination tests, detected by nephelometry. Serum SAA concentrations were higher in overweight/obese (P = 0.008) patients and this condition was dependent on obesity (BMI and waist circumference), as further shown by multivariate linear regression analysis done for SAA (P = 0.01). Concentrations of SAA were also higher in patients with estrogen receptor-negative (ER(-)) tumors than in those with estrogen receptor-positive (ER(+); P = 0.033). Our results suggest a possible role for SAA in the development and prognosis of obesity-related breast cancer. A follow-up study of this population to assess overall and disease-free survival is in course and should bring contribution to evaluate the clinical role of SAA in breast cancer in the context of obesity.