The relationship of estrogen receptor (ER) status to DNA ploidy was investigated in 121 patients with breast cancer who underwent surgery. Lymph node status was evaluated histologically and ER levels were determined by the dextran-coated charcoal method, with a level of 3 fmol/mg.protein being considered positive. Flow cytometric DNA content was analyzed using paraffin-embedded tissue blocks. Sixty-three percent of the specimens were ER+, while 37 percent were negative. Sixty-one patients (50.4 percent) were diploid and 60 aneuploid. A statistically significant correlation between the ER positivity rate and diploid DNA was found. Higher ER levels were seen in the postmenopausal patients with diploid tumors than in those with aneuploid tumors and there was a significant tendency for ER levels to be higher in the diploid tumors. Nodal status was not correlated with ER positivity or ploidy pattern. The present results indicate that ER levels are correlated with DNA ploidy, and reflect the degree of functional differentiation.