A recent proposal of tight coupling between evolution of fibroblast growth factor (FGF) signaling and evolution of the vertebrate head underscores the importance of FGFs and their receptors (FGFRs) in cranial variation. Mutations in FGFRs cause achondroplasia and some craniosynostosis syndromes, establishing an essential role for FGF signaling in endochondral and intramembranous bone development. But there is more to the vertebrate head than the skull, and many tissues undergo dramatic change during head evolution and morphogenesis although the association of FGF signaling with variation in other cranial tissues is less well understood. Our objective is to estimate pattern and magnitude of variation in the skull and other head tissues produced by several craniosynostosis syndrome‐causing FGFR2 and FGFR3 mutations to produce hypotheses about their role in head evolution. We use 3D micro‐CT imaging and magnetic resonance microscopy to estimate variation in cranial tissues of mouse models for human craniosynostosis syndromes and identify local effects of these mutations on neural, epithelial and osseous cranial tissues. Our results reveal strong parallels between mouse and human phenotypes carrying corresponding FGFR mutations emphasizing the conservation of FGF/FGFR function in development and suggesting mechanisms of head evolution. Supported by NIH/NIDCR grants 5 R01 DE018500, ‐02S1, ‐02S2.