A review of assay results from more than 5500 patients revealed 283 patients in whom multiple breast cancer specimens were analyzed for progesterone receptor (PGR). All assays were performed in a single laboratory between 1975 and 1982 using the sucrose gradient technique. We considered only the 8S fraction of PGR. Simultaneous assays in 109 patients yielded 14% discordance [one assay with greater than 10 fmol/mg cytosol protein (PGR+) and one assay with less than 5 fmol/mg protein (PGR-)]. Among 161 sequential assays, there was an overall discordance of 19%: 8% (nine of 106) when the initial assay was PGR-, but 44% (24 of 55) when the initial assay was PGR+. Among PGR+ patients initially assayed at the time of diagnosis, there was a tendency to greater receptor loss in patients with positive axillary lymph nodes (44 versus 11%). The length of time between biopsies did not increase the discordance, but endocrine therapy within this interval did increase it (56% of initially PGR+ patients who received interim endocrine therapy were PGR- at second biopsy). to evaluate the significance of interval loss of PGR, we compared survival from first biopsy in initially PGR+ patients who subsequently lost their receptor versus those whose receptor persisted. The latter group experienced a significantly longer survival (p less than 0.02). In summary, we observed an ominous loss of PGR in sequential biopsies, particularly with intervening endocrine therapy, and those patients whose tumor cells lost PGR experienced poorer survival than did patients retaining PGR. Therefore, patients with PGR+ primary tumors require repeat biopsy for PGR upon disease recurrence for optimal treatment planning.