Ductal carcinoma in situ (DCIS) of the breast represents a proliferation of malignant epithelial cells within the ducts and lobules of the breast, without invasion through the basement membrane. It is believed that all invasive carcinomas are preceded by DCIS; however, it is not known what proportion of patients with DCIS will develop invasive carcinoma and after what interval. DCIS is heterogeneous with respect to its clinical presentation, mammographic abnormalities, histology and biology. The risk of progression to invasive carcinoma depends on the histologic type of DCIS and the size of the lesion; in the future, the analysis of the genetic alterations may also help in predicting the risk of progression to invasive breast cancer. As the risk of progression to invasive breast cancer (and the development of metastases) greatly influences the choice of treatment for DCIS, it is of importance to be able to make a reliable estimate of this risk of progression. In this chapter, the histologic classification of DCIS and the genetic alterations that have been found to date are discussed.