Summary The trunk of fish is covered by a large variety of morphologically and structurally diverse skeletal elements, such as scales, scutes and bony plates . These elements are formed from intramembraneous ossifications and are part of the integumentary skeleton . Histological and developmental similarities with neural crest-derived teeth in fossil and extant vertebrates, have led to the widely accepted notion that scales and fin rays, which are thought to be a scale modification, primarily derive from neural crest and not from mesodermal sources as the majority of the post-cranial skeleton . Although short- and long-term labeling experiments in zebrafish have suggested a neural crest origin of fin rays [3,4], the contribution of neural crest to the post-cranial integumentary skeleton, and in particular to the scales, has not been thoroughly analyzed. By Cre/loxP-based genetic labeling, transplantation experiments and transposon-mediated clonal analysis, we demonstrate a mesodermal origin of scale-forming osteoblasts. Furthermore, our data do not support an extensive, if any, neural crest contribution to the post-cranial integumentary skeleton.