Stefano Fais and Michael OverholtzerAbstract | Cell-in-cell structures are reported in numerous cancers, and their presence is an indicator for poor prognosis. Mechanistic studies have identified how cancer cells manage to ingest whole neighbouring cells to form such structures, and the consequences of cell-in-cell formation on cancer progression have been elucidated. In this Opinion article, we discuss how two related cellin-cell processes, cell cannibalism and entosis, are regulated and how these mechanisms promote cancer progression. We propose that cannibalistic activity is a hallmark of cancer that results in part from selection by metabolic stress and serves to feed aggressive cancer cells.