Summary The relationship between DNA content of mammary cancer and subsequent response to endocrine therapy was studied in 136 patients with advanced disease. All were treated with tamoxifen or ovarian ablation as first-line systemic therapy after relapse and were evaluable for response according to UICC criteria. DNA characterisation by flow cytometry was used on formalin fixed paraffin-embedded samples of tumour. Tumours were grouped according to DNA index into diploid (n = 52, 38%), 'tetraploid' (n =46, 34%) and 'other DNA-aneuploid' (n=38, 28%). The highest proportion of oestrogen receptor positive tumours (ER+ve) was found in the 'tetraploid' tumours (38/46, 85%, Chi-square=8.53, P<0.02), and response rates, (SD + PR+CR), were 26/52 (50%), 34/46 (74%), and 15/38 (39%) respectively (Chi-square= 10.88, P<0.005). Patients with diploid or 'tetraploid' tumours survived longer and stayed in remission longer than those with other DNA-aneuploid' tumours. We suggest that 'tetraploid' or 'near tetraploid' human mammary tumours may comprise a distinct group of endocrine responsive tumours within the overall group of aneuploid tumours. The conventional interpretation of DNA histograms, grouping into diploid and aneuploid, may be masking important features of some tumour groups.In the past cellular DNA ploidy was assessed by the use of nucleic acid specific stains on tissue sections and microdensitometry. Only relatively small numbers of cells could be assessed. The development of flow cytometry (FCM) has brought a rapid and reproducible technique for determination of DNA content of tumours. Thousands of nuclei can be evaluated, and DNA histograms produced which indicate different cell populations.