Abstract Ductal carcinoma in situ (DCIS), breast cancer confined to the milk ducts, is a heterogeneous entity. The question of how and when a case of DCIS will extend beyond the ducts to become invasive breast cancer has implications for both patient prognosis and optimal treatment approaches. The natural history of DCIS has been explored through a variety of methods, from mouse models to biopsy specimen reviews to population-based screening data to modeling studies. This article will review the available evidence regarding progression pathways and will also summarize current trials designed to assess DCIS progression.