Background: Reptiles have been suggested to be a suitable model for the histological and histochemical aspects even better than other used experimental mammals. Melanomacrophage centers (MMCs) are aggregations of macrophage-like cells and pigments including melanin, hemosiderin, and lipofuscin. MMCs found mainly in different tissues of non-mammalian vertebrates. MMCs are helpful biomarkers for a variety of stresses as environmental pollutants. Aim: This study was designed to elucidate the histological, morphometric, histochemical and immunohistochemical characterization of hepatic MMCs in three reptilian species; Uromastyx ornata (Ornate Dabb lizard), Uromastyx aegyptiaca (Egyptian Dabb lizard), and Varanus griseus (Desert Monitor lizard). Methods: Fifteen adult male reptilian animals were divided into; i. Five adult males Ornate Dabb lizard, ii. Five adult males Egyptian Dabb lizard, iii. Five adult males Desert Monitor lizard. Liver paraffin sections of all animals were processed and stained with Hematoxylin and Eosin stain, Masson Trichrome stain for collagen fibres and Perl's Prussian Blue histochemical stain for hemosiderin pigments. Immunohistochemical demonstration of melanin pigments via HMB-45 and macrophage lineage via CD68 immunostains were applied. Histomorphometric assessments of MMCs were also performed. Results: Histomorphometric examinations revealed significant differences between the histomorphometric structures of MMCs among the experimented species.  MMCs in Desert Monitor lizard were fewer in number and smaller in size; with decreased melanin pigment contents and macrophage lineages, and increased hemosiderin contents. Conclusion: The significant differences in MMCs among the three reptiles may indicate considerable differences between the immune system of the Desert Monitor lizard and each of the Ornate and Egyptian Dabb Lizards.