Epidermal growth factor receptor (EGFR) and estrogen receptor (ER) were assayed by ligand binding in tumors from 370 patients with primary breast carcinoma with a median follow up of 18 months. Forty seven percent (175/370) and 57% (210/370) of tumors had > 20 fmol/mg and > 10 fmol/mg of EGFR and ER respectively. There was a highly significant inverse relationship between EGFR and ER (p = 0.0032). There was also a significant association between EGFR and patient age (p = 0.0006) but not correlation between EGFR and lymph node status, tumor grade, or tumor size (p = 0.104, p = 0.198, and p = 0.085 respectively). In a univariate analysis of all patients, EGFR expression was not associated with a significant reduction in overall survival (OS). However, there was a significant decrease in relapse-free survival (RFS) and OS in node negative EGFR positive patients (p = 0.03 and p = 0.05 respectively). In a multivariate analysis (Cox proportional hazard model) of all patients, lymph node status was an independent prognostic indicator for OS and RFS (p < 0.00005) and p = 0.00005 respectively), ER status for RFS (p = 0.0006), and EGFR (in the node negative model) for RFS (p = 0.03). When all patients were stratified for EGFR and ER, there was a significant difference in RFS and OS such that EGFR positive and ER negative had the worst prognosis (p = 0.0034 and p = 0.005 respectively).