Assessment of cancer risk, particularly with a view toward targeting strategies for prevention, is a recent development. The future will see the garnering of more specific information about determinants of risk and their interaction with screening prevention and therapeutic modalities. We are not a full professional generation removed from a time when the question of malignancy in the breast was absolute, yes or no. Now special types of breast cancer are recognized that pose little threat to life, while some benign conditions indicate greatly increased risk of death from cancer. Comparisons of premalignant determinants in other organ systems indicate that cytologic, histologic, and metaplastic features may be more or less important in different organs. Their separate and combined analysis as predictors give a complex measure of tissue organization, which is often predictive of concurrent cancer and/or future cancer development. In proliferative breast disease, the markers of cancer risk may be classified into histologic categories of slightly, moderately, and markedly increased risk. In cases of slightly increased risk, the probability for cancer development is 1.5 to 2 times that of the general population; a moderately increased risk denotes that the likelihood of cancer development may be 4 to 5 times greater; a markedly increased risk has a predictive value of 9 to 10 times that of the general population.