Associated with the age-dependent role change of worker honeybees (Apis mellifera L.) from nurse bees to foragers, some structural and functional changes occur in the hypopharyngeal glands (HPGs): nurse bee HPGs are well developed and synthesize major royal jelly proteins (MRJPs), while forager HPGs shrink and synthesize α-glucosidase, which converts nectar into honey. To identify candidate genes involved in the structural and functional HPG changes associated with the age-dependent role change of worker honeybees, we searched for genes whose expression in the HPGs depends on the role of workers, by using differential display and quantitative reverse transcription-polymerase chain reaction. Here, we newly identified a buffy homolog encoding a Bcl-2-like protein as a gene whose expression, like MRJP, is higher in nurse bees than in foragers, and a matrix metalloproteinase 1 (MMP1) homolog as a gene whose expression, like α-glucosidase, is higher in foragers than in nurse bees, suggesting that both suppression of inhibition of the caspase cascade by buffy and degradation of the extracellular matrix by MMP1 are involved in the functional and structural changes of the HPGs. Furthermore, although both buffy and MMP1 were highly expressed in various tissues other than the HPGs, buffy expression in the other tissues did not differ significantly between nurse bees and foragers, whereas MMP1 expression in midgut was also significantly higher in foragers than in nurse bees, as in the HPGs. These results suggest that in buffy and MMP1, expression is regulated in a tissue-preferential manner according to the age-dependent role change of workers.