Tumor samples obtained from 106 primary breast cancer patients were examined biochemically (DCCA) and immunohistochemically (IHC) for estrogen (ER) and progesterone receptors (PR) to assess a quantitative relationship between both assays and to study the influence of the tumor-stroma ratio on this quantitative relationship. We used a model of logit transformation of IHC values (% of positive cells) and logarithmic transformation of DCCA values (fmol receptor/mg cytosolic protein). Tumors were subdivided into three categories according to the tumor-stroma ratio (more (t > s), equal amounts (t = s) or less (t < s) tumor than stroma), and the influence of the tumor-stroma ratio was studied using multiple regression analysis. We report a mathematical relationship between the results of the biochemical and immunohistochemical assays for the determination of ER status and PR status in primary breast cancer patients (ER: log DCCA(fmol/mg) = 0.369 logit (IHC(%pos cells)) + 2.328 (r = 0.573; p < 0.0001); PR: log DCCA (fmol/mg) = 0.474 logit (IHC(%pos cells)) + 0, 00 (r = 0.634; p < 0.0001)). In tumors overexpressing ER immunohistochemically (>10% nuclear positivity), median ER-DCCA is significantly higher if the tumor-stroma ratio is greater than 1. As these patients respond to hormonal treatment, depending on the degree of expression of both receptors, this study suggests that the biochemical assay be avoided because this technique is hampered by false-negative or falsely low results due to the loss of morphological information on the tumor-stroma ratio.