Epidermal Growth Factor Receptor (EGFR) expression has been studied extensively for its prognostic value, yet large overviews still indicate that it has no prognostic significance in contrast to data from individual studies (1). Several reasons account for this such as differences in sample size, study design and methodology, influence of adjuvant therapy, and short follow-up. To help address some of these issues, we examined a historical series of 254 cases of primary operable breast cancer in women receiving no adjuvant therapy where long-term follow-up (median, 180 months) was available. All cases were ages <70, well characterized with triple node sampling, and had been followed up annually. EGFR status was determined using routine immunohistochemistry (E30 antibody; Biogenix) and a semiquantitative scoring system: 0, 1, 2, 3 [2 and 3 were considered positive (cytoplasmic staining)]. Eighty-two (n = 82) tumors showed positive immunoreactivity (32%). Univariate analysis showed no significant difference between EGFR status and tumor size or type, but significant associations with lymph node stage (P = 0.05), estrogen receptor (P < 0.001) and histologic grade (P < 0.001) were seen. In multivariate analysis with stage, grade, EGFR, and estrogen receptor included, only stage and grade were independently significant for disease-free survival. For overall survival, the prognostic effect of grade and stage persisted and only in lymph node positive disease was EGFR independently significant (P = 0.008) for a survival advantage.We believe that there are important differences between studies that continue to plague the identification of patients who may benefit from EGFR testing. Tsutui et al. (2) recently reported on the EGFR status of 1029 patients, stating that EGFR had independent significance; however, this dataset included the confounding influence of adjuvant therapy, with short follow-up and grade was not assessed.Ferrero et al. (3) examined a similar size set (n = 780) and found EGFR to have no prognostic significance. We found EGFR to be significant only in lymph node-positive disease and when compared with traditional histopathological prognostic factors such as grade, size, and lymph node stage, the β coefficient was small (0.2), indicating that the pure prognostic impact of EGFR status is insignificant in routine practice compared to histological factors.