Pancreatic ductal adenocarcinoma (PDAC) comes in two subtypes, one referred to as basal-like (or squamous) and the other denoted classic (or progenitor). The two types have markedly different gene-expression profiles and carry different prognoses, with basal-like PDAC being more aggressive. Miyabayashi and colleagues developed a novel mouse model in which PDAC organoids are engrafted into the pancreatic ducts, where PDACs develop in humans, and PDACs grown in this way recapitulated the two subtypes observed in patients. Analyses of these tumors revealed that cell plasticity–mediated switching between the subtypes could occur, and the transition from a classic-like to a basal-like subtype was associated with activation of genes in the KRAS pathway. For more information, see the article by Miyabayashi and colleagues on page 1566.