Aims: Pancreatic beta cells are known to share many similarities with neuronal cells, but their origin remains controversial. It has been hypothesized that pancreatic beta cells are derived from neural crest cells. The aim of this study was to investigate the similarities between pancreatic beta cells and cells with neural crest, endoderm and mesoderm origin with respect to c-Fos immunoreactivity (c-Fos-ir), which has a role in important cellular processes including cellular proliferation, growth, differentiation and apoptosis. Methods: c-Fos-ir was analyzed by immunohistochemical methods in formaline-fixed, paraffin-embedded sections of rat pancreatic beta cells (BCs), in adrenal medullary chromaffin cells (CCs) that are derived from neural crest, in exocrine pancreatic acinar cells (ACs) that are derived from endoderm, and in adrenal cortex zona reticularis cells (RCs) that are derived from mesoderm. Results: The statistical comparisons revealed no significant differences between BCs and CCs with respect to c-Fos-ir (p>0.05). However, a highly significant difference (p<0.001) with respect to c-Fos-ir both between ACs and RCs, and between these two cell types and each of the two other cell types was noted. Conclusions: As opposed to findings in cells without neural crest origin, the observed similarity between BCs and CCs with respect to c-Fos-ir, provides additional evidence for the similarity of these cells with cells derived from neural crest. (C) 2004, Editrice Kurtis.