Developing cells acquire mature fates in part by selective (i.e. qualitatively different) expression of a few cell‐specific genes. However, all cells share the same basic repertoire of molecular and subcellular building blocks. Therefore, cells must also specialize according to quantitative differences in cell‐specific distributions of those common molecular resources. Here we propose the novel hypothesis that evolutionarily‐conserved transcription factors called scaling factors (SFs) regulate quantitative differences among mature cell types. SFs: (1) are induced during late stages of cell maturation; (2) (...) are dedicated to specific subcellular domains; and, thus, (3) allow cells to emphasize specific subcellular features. We identify candidate SFs and discuss one in detail: MIST1 (BHLHA15, vertebrates)/DIMM (CG8667, Drosophila); professional secretory cells use this SF to scale up regulated secretion. Because cells use SFs to develop their mature properties and also to adapt them to ever‐changing environmental conditions, SF aberrations likely contribute to diseases of adult onset. (shrink)