The purpose of this study was to assess the potential value of large-needle core biopsies of normal breast tissue for immunohistochemical studies of epithelial risk assessment. A retrospective analysis was performed to determine the yield of nonatrophic terminal duct lobule units (TDLUs) in 11-gauge vacuum-assisted core biopsies of normal adjacent breast tissue which were included in routine stereotactic core biopsies of benign lesions. Fifty-one patients had a median of two normal tissue cores (range 1-7); 82% of the patients had two or more normal tissue cores; 47% had three or more normal tissue cores. Nonatrophic TDLUs were present in only 47% of patients and in 31% (42 of 137) of all cores. Patients with heterogeneous or dense normal mammographic parenchyma at the site of the biopsy were more likely to have nonatrophic TDLUs, 45% (20 of 44), than patients with fatty normal mammographic parenchyma at the biopsy site, 0% (0 of 7), p = 0.007. Seventy percent (7 of 10) of postmenopausal women on hormone replacement therapy had nonatrophic TDLUs as compared to 41% (11 of 27) of premenopausal and postmenopausal women not on hormones (p = not significant). Eleven-gauge vacuum-assisted core biopsies of normal breast tissue have a low yield of nonatrophic TDLUs suitable for histochemical studies of epithelial risk assessment.