ABSTRACTAfter decades of research, our knowledge of the complexity of cancer mechanisms, elegantly summarized as ‘hallmarks of cancer’, is expanding, as are the therapeutic opportunities that this knowledge brings. However, cancer still needs intense research to diminish its tremendous impact. In this context, the use of simple model organisms such asCaenorhabditis elegans, in which the genetics of the apoptotic pathway was discovered, can facilitate the investigation of several cancer hallmarks. Amenable for genetic and drug screens, convenient for fast and efficient genome editing, and aligned with the 3Rs (‘Replacement, Reduction and Refinement’) principles for ethical animal research,C. elegansplays a significant role in unravelling the intricate network of cancer mechanisms and presents a promising option in clinical diagnosis and drug discovery.