Many breast cancer (BC) cases are detected with advanced stages and thus worse prognosis. Thus, evaluating sensible biomarkers for BC early detection and prognosis is still a great challenge. Here, we aimed to evaluate the association between serum amyloid A (SAA) and both detection and prediction of poor BC progression. Compared to CEA and CA 15.3 as established tumor markers, our findings found that elevated SAA significantly (P<0.0001) related to BC development (36.74 (21.1-50.2) ng/mL) compared to patients with benign diseases (14.3 (12.0-18.12) ng/mL) and healthy (5.1 (3.2-6.9) ng/mL) controls. It had a great ability (AUC=0.960) to diagnosing BC patients. SAA levels (ng/mL) was significantly (P<0.05) affected the disease progression including tumor late stages (47.3 (37.0-90.5)), lymph node invasion (40.8 (27.5-69.23)), distant metastasis (75.0 (47.8 108.0)), high grades (78.5 (24.8-100.2)) and large size (41 (28.9-71.2)). Moreover, SAA high levels were associated to negative estrogen receptor and progesterone receptor status and negative HER2. SAA was significantly correlated with CA 15.3 (r=0.317; P=0.0020) and CEA (r=0.644; P=0.0001) in BC patients. In conclusion, SAA protein appears to have a pivotal role in BC development and progression. Owing to the association between its increased concentrations and BC severity, it could be a biomarker candidate for BC surveillance and perhaps a therapeutic BC target.