The aim of the present study was to analyze the distribution and characteristics of NPY immunoreactive structures in the cerebral cortex of lizards and to investigate the degree of co-existence of this neuropeptide with somatostatin and GABA. The immunoperoxidase method was applied to vibratome sections as well as to semithin sections. NPY neurons are multipolar or fusiform and were unevenly distributed throughout the brain cortex. Within the medial, dorsomedial and dorsal cortices, most NPY perikarya were located in the plexiform layers, especially in the deep one. This suggests that these cells could be regarded as interneurons. In the lateral cortex, NPY neurons were found throughout all layers. The dorsomedial cortex displayed the highest NPY cell density. Here, neuronal perikarya projected many immunoreactive processes toward two distinct zones: the deep plexiform layer of the medial cortex and the superpositio medialis. The NPY neurons of the dorsomedial cortex differed from the other NPY cortical immunoreactive cells in that the latter displayed very few immunoreactive processes. A high degree of co-existence among NPY, somatostatin, and GABA (approx. 80%) was found. This co-existence rate is very similar to that reported in mammals and suggests that co-localization is a phylogenetically ancient phenomenon.