Within a population-based breast cancer screening programs, 209 cancers were detected by regular mammographic screening. Additionally, 66 cancers were discovered between two consecutive screenings after one, two, or three negative screening examinations (interval cancers). The study group consisted of 25,920 women who have been participating since 1975 in a breast cancer screening program in Nijmegen, the Netherlands. In this program, single view mammography (lateromedial projection) was administered as the sole screening examination every two years. Physical examination was not part of the screening program. All previous histologic and radiologic material from 64 of those "interval" patients was available and was reviewed. In 19 of the 64 patients, direct or indirect signs of tumor were seen on the previous screening mammogram on review (observers error). In four cases the site of the tumor lay outside the imaging field (technical error). In 41 cases, no signs of tumor could be seen on the mammograms even on review. By calculated tumor doubling times, 20 of these 41 cases were probably too small to be detected at the last screening ("real" interval cancers). However, 21 cases were probably large enough but were somehow masked from radiologic detection. The mean reasons for this "masking" proved to be: 1) dense breast, 2) poorly outlined tumor mass of diffuse infiltrative type, mainly invasive lobular carcinomas, and 3) intraductal localization. The authors suggest that women with dense breasts be screened more frequently, using more views and modalities and with broader criteria for advising surgical biopsy. They also note that in general the two-year interval between screenings is probably longer than the optimal interval.