This study has shown that a DCIS-associated malignant pathway can occur in patients who have pathogenic variants in BRCA2, CHEK2, PALB2, BRCA1 and TP53. We also show that the focus of genetic testing should be on ER-positive, intermediate-, and high-grade DCIS from patients under the age of 40, rather than ER-negative DCIS, although restricting such testing to those age under 40 would fail to identify the majority of CHEK2 and PALB2 mutation carriers. Here, PALB2 is linked to ductal breast carcinoma in situ.