ARTICLE ABSTRACTMany patients develop cancers that have clinical features of inherited syndromes (e.g., young age of onset and unique pathology) but lack mutations in the genes characteristic of the disease. In this issue of the journal, Wong et al. report that somatic epigenetic inactivation could explain some such cases in the setting of BRCA1-associated breast cancer. Here, we discuss the implications of this work in terms of the etiology, risk, and potential prevention of cancer. Cancer Prev Res; 4(1); 6–8. ©2011 AACR.