In 2005/2006 the German National Mammography Screening Program was initiated and has now become established. The objective is to reduce breast cancer mortality and the early diagnosis and therapy of small cancers. The program follows the European guidelines and is controlled by over 30 parameters of quality. All trained members of the team document each step of the screening chain electronically. Histological assessment (HA) is recommended in up to 2% of examinations, 90% of HAs are performed by core needle biopsy (CNB) or by stereotactic vacuum-assisted biopsy (VABB). Open diagnostic biopsies are performed in <10% of all HAs and therapy is successful in some of the B3 lesions. Mammograms are interpreted by two independent readers. Recommendations of the regular interdisciplinary conferences, preoperative and postoperative, follow the European guidelines. About 45% of all breast cancers detected by screening are in-situ or less than 10 mm in size. The 17% alterations diagnosed by needle biopsy are B3 or B4 lesions and impose high demands on the pathologists and the interdisciplinary team. Due to the many early and discrete lesions counterchecking of representative biopsies is crucial. Problems may be caused by sampling error or partial volume effects. Interdisciplinary conferences and knowledge of the limitations of each discipline and method are needed to optimize diagnostic and therapeutic decisions.