This investigation was conducted to assess the predictive value of calcifications and densities in mammograms from women <50 years of age for subsequent diagnosis of breast cancer. In a population-based study, prior screening mammograms taken before age 50 in 547 women with breast cancer and 472 controls were reviewed by a single radiologist. The relative risk (RR) of subsequent breast cancer increased with the percentage of the area of the mammogram that was mammographically dense [RR in succeeding quartiles of density = 1.0, 1.7 (1.1-2.6), 3.3 (2.2-5.0), and 4.0 (2.7-6.0)]; in relation to Wolfe parenchymal pattern class P2 [RR = 3.1 (2.2-4.3)] or DY [RR = 5.6 (3.2-10.0)]; and in relation to calcifications of class 1 (pleomorphic of any distribution) or class 2 (various morphological types that are regional, grouped, clustered, segmental, or linear in distribution) [RR = 3.0 (1.4-7.1), and 1.8 (1.2-2.6), respectively]. Women with radiographically dense mammograms and class 1 or 2 calcifications were at >10- and approximately 6-fold greater risk, respectively, than women with breasts of low density and no calcifications. Densities and parenchymal patterns were most strongly associated with breast cancer being diagnosed in the next 3 years. Class 1 and 2 calcifications were most strongly predictive of an increased risk in 3-6 years. Class 1 calcifications were strongly predictive of the breast in which the subsequent cancer occurred. Women <50 years of age with class 1 or 2 calcifications or mammographically dense breasts, or both, should receive high priority for further evaluation and regular breast cancer screening.