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 and 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.