Epidermal growth factor (EGF) seems to play an important role in regulating the proliferation of human breast cancer. Fifty-five primary breast tumors and 7 lymph node metastases were simultaneously assayed for the presence of EGF receptors (EGFR), estrogen receptors (ER), and progesterone receptors (PR). Overall, 42% (23/55) of the tumors were EGFR positive. EGFR were more frequently present in ER- and PR-negative than in ER- and PR-positive tumors. In particular, a negative correlation between EGFR and PR (chi 2 = 6.8; p greater than 0.01) was observed. All metastatic tumors were EGFR negative, and in all cases but 1 the levels of EGFR were higher in metastatic than in primary tumors. Our results suggest the presence of a subclass of breast tumors, the growth of which is primarily regulated by EGF or EGF-like substances rather than by steroid hormones. In this group, not amenable to endocrine therapy, EGF receptors should represent a target for therapeutic intervention.