The prognostic value of Epidermal Growth Factor Receptor (EGFR) in human breast cancer is a matter of debate. We conducted a prospective study that included 459 unselected patients with primary breast cancer (median follow-up 24 months) to assess the prognostic value of EGFR. EGFR was assessed using a standardized radioligand binding assay. Univariate analysis showed that EGFR is a factor indicative of a poor prognosis with respect to Disease Free Survival (DFS, P = 0.03) and Overall Survival (OS, P = 0.002), if an EGFR level of 50 fmol/mg of membrane protein is introduced as a cut-off for EGFR-positivity. Multivariate analysis showed that EGFR was not an independent factor. This prospective study shows that EGFR, although not an independent factor, is indicative of poor prognosis in human breast cancer.