Primary (neoadjuvant) chemotherapy of locally advanced breast carcinomas is performed to locally reduce the tumour mass and to improve the operability. Recently, the indication for primary chemotherapy has been extended for preoperative treatment in breast conserving surgery. In an ongoing clinical trial we examined the resection specimens of 51 mammary carcinomas after primary chemotherapy. These patients had received a neoadjuvant therapy with epirubicin/cyclophosphamide for size reduction of large (> 3 cm) but operable tumours (pretreatment median tumour size 4.5 cm by mammography). The tumour response was evaluated pathologically and compared with the clinical tumour regression that was observed in over two-thirds of all cases. We classified the regressive changes using a semiquantitative scoring system from 0 to 4 (0 = no effect, 1 = resorption and tumour sclerosis, 2 = minimal residual invasive tumour [< 0.5 cm], 3 = residual noninvasive tumour only, 4 = no tumour detectable). The aim of this study was to evaluate the improvement of operability objectively and to correlate the histology of the primary tumour with the response to treatment. With invasive lobular carcinomas, the tumour size after therapy was reduced less than average and irrespective of the amount of histological tumour cell reduction, largely due to the stromal content of these neoplasms. Invasive ductal carcinomas with extensive or predominant intraductal component also underwent only a slight decrease in tumour size; this was because of the lack of tumour response with the intraductal component. Well differentiated tubular carcinomas were particularly resistant to primary chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)