Image cytophotometric DNA analysis of atypical hyperplasias and intraductal carcinomas of the breast. With the use of image analysis, DNA content was quantified on paraffin-embedded tissue sections of 25 atypical hyperplasias and 35 intraductal carcinomas of the breast by comparison of integrated gray levels of Feulgen-stained control and ductal cell nuclei. The mean full-peak (G0/G1) control cell DNA histogram coefficient of variation was 5.5%. DNA aneuploidy was more common in intraductal carcinomas compared with atypical hyperplasias (71% of intraductal carcinomas vs 36% of atypical hyperplasias) and correlated with a lack of cytologic (nuclear) and architectural differentiation (63% moderate vs 93% poor and 38% cribriform vs 82% solid). In addition, multiple DNA stemlines were observed in 40% of intraductal carcinomas. We conclude that (1) some atypical hyperplasias demonstrate abnormal DNA content consistent with neoplastic transformation, (2) aggressive forms of intraductal carcinoma are more frequently associated with DNA content abnormalities, and (3) frequent DNA stemline heterogeneity in intraductal carcinoma supports the hypothesis that multiple genetic events occur in the development of mammary intraepithelial neoplasia. 