Abstract Epidermal growth factor receptor (EGFR) plays an important role in the pathogenesis of multiple malignancies and its expression strongly also affects the outcomes of cancer patients. The objective of this study was to determine the clinical significance of the serum levels of EGFR in breast cancer (BC) patients. A total of 96 patients with a pathologically confirmed diagnosis of BC were enrolled into this study. Serum EGFR levels were determined by the solid-phase sandwich ELISA method. Age and sex matched 30 healthy controls were included in the analysis. Median age of diagnosis was 48years old (range: 29–80). Thirty-seven (39%) consisted of metastatic disease. The baseline serum EGFR levels were significantly higher than in the healthy control group (p<0.001). The serum EGFR concentrations were also significantly higher only in patients with ER-negative and triple-negative tumor (p=0.05 and p=0.04, respectively). The other known clinical variables, including grade of histology, stage of disease, serum CA 15.3 levels, and response to chemotherapy were not found to be correlated with serum EGFR concentrations (p>0.05). Likewise, serum EGFR levels were found to play no prognostic role for survival (p=0.35). In conclusion, while serum EGFR levels were elevated in BC patients, EGFR level has no predictive and prognostic value in these patients.