In general, failure to detect or correctly characterize breast cancer can be attributed to one of four main factors: inherent limitations of screen-film mammography, inadequate radiographic technique, subtle or unusual lesion characteristics, and interpretation error. The restricted latitude and display contrast of screen-film mammography are among the significant factors that result in decreased visualization of breast tumors and microcalcifications in patients with dense fibroglandular tissue. Unlike the inherent limitations of screen-film mammography, a poor radiographic technique can be improved on and should be eliminated. Crucial components of a well-performed mammographic examination are correct positioning, adequate compression, and proper image exposure. Lesion characteristics that may lead to a false-negative mammogram include small size, a site where visualization is difficult, visualization on only one view, a benign or probably benign appearance, lack of a desmoplastic reaction, and slow or no apparent growth. Causes of interpretation error include suboptimal viewing conditions, outside distractions, lack of a systematic approach, oversight of a subtle lesion because of an obvious finding, lack of knowledge of clinical findings, imprecise correlation with results of other studies, and nonbelief. Recognition of these various factors should help decrease the rate of false-negative mammograms.