The neocortex is the part of the brain responsible for higher-order functions including behavioural diversity and complexity. It is unique to mammals, but there are subtle differences in neocortex structure between marsupials and eutherians. This contrasts with the rest of the brain anatomy, which is highly conserved. In this Issue, Linda Richards, Laura Fenlon and colleagues compare the developing neocortex of the mouse-sized marsupial Sminthopsis crassicaudata (fat-tailed dunnart) with that of the eutherian mouse. Using a de novo assembled transcriptome from the dunnart and published data from the mouse, the authors analyse gene expression changes in early and late stages of cortical development, when neurons from equivalent neocortical layers are being born. They find that, during early development, the dunnart transcriptome is enriched for genes responsible for neuronal differentiation and function, whereas the mouse transcriptome is enriched for genes associated with a progenitor state. Further, although the mouse gene expression profile changes from early to late development, with a progression towards neural differentiation, there are few changes in the dunnart expression profile between the two stages. Together, these data indicate that key differences exist in neocortex development between marsupials and eutherians; neuronal differentiation in the dunnart begins earlier than in the mouse but is more protracted.