We have examined the appearance of c-erb-b2 and int-2 amplification in 2 different groups of breast-cancer patients. The groups differed with regard to their clinical status in that one group was receiving first-line endocrine treatment (tamoxifen) whereas the second was receiving second-line endocrine treatment (after failing on tamoxifen). The latter group of patients showed clinicallya a more advanced disease (higher frequency of stage-IV as compared to stage-III disease). Consecutive tumor samples were obtained using fine-needle biopsies from individual tumor lesions of each patient every second or third month. Median time from diagnosis to the last biopsy for patients receiving tamoxifen was 25 months and, for patients receiving second-line treatment, 55 months. The presence of amplification was determined using semi-quantificative PCR. We found that both genes developed amplification during tumor progression. The appearance of amplification was more pronounced in the clinically more advanced patients receiving second-line treatment (p = 0.018).