Ionic regulation is essential for the metabolism and cellular function. For many physiological processes, ionic calcium (Ca(+2)) is important for example muscle contractions, nerve signaling, membrane permeability, cell division and hormone release. In nerve cells, the excess intracellular concentration of Ca(+2) causes cell death. It has been shown that certain calcium binding proteins (CaBPs) are essential for Ca(+2) homeostasis and protect neurons from excess Ca(+2) influx. We are for the first time showing an unusual calretinin (CR) expression and significant differences in its occurrence in the forebrain of the cichlid fish (Cynotilapia sp.) compared to other teleosts. CR labeled neurons were seen in the dorsal and lateral part of the dorsal telencephalic area, entopeduncular nucleus (EN), nucleus preopticus (NPO), diffuse nucleus of lateral torus (NDTL), ventral hypothalamic nucleus (VH), preglomerular nucleus (NPG) and optic tectum. Surprisingly, large numbers of CR immunoreactive perikarya were noted in the optic chiasma (Oc). These neurons were oval with elongated processes and forming a huge fiber network in the Oc. Enormously CR stained fibers were seen in the lateral and medial olfactory tract. Widespread distributions of strongly CR labeled fibers were observed around the EN projecting dorsally into the telencephalon, Oc and optic nerve. Presence of CR in the NPO suggests that it may be involved in the hormonal regulation by the pituitary. As in vertebrates EN plays an important role in sensory functions, massive localization CR in the EN may suggests role of CR in sensory functions of the cichlid fish.