pS2 protein expression is induced by estrogen through estrogen receptors (ER), and is known to be inhibited by antiestrogen in the breast cancer cell line MCF-7. The present study was undertaken to determine whether pS2 expression may be inhibited by the antiestrogen tamoxifen (TAM) human breast cancer. pS2 expression was immunohistochemically investigated in 22 patients treated preoperatively with TAM and in 45 without TAM treatment (control group). Immunostaining was considered positive when 10% of tumor cells showed cytoplasmic staining. We found that 94% of the pS2-positive tumors were ER-positive (ER+), and there was a significant association between the two proteins (p < 0.0001). In ER+ tumors, pS2 expression was seen in only 21% (3 of 14) of the TAM+ group, compared to 70% (16 of 23) of the control group. Statistical analysis of these data indicated a high likelihood (p = 0.006) of TAM treatment being associated with inhibition of pS2 expression in human breast cancers.