<p>We have analyzed by immunohistochemical methods the Oberhautchen-beta layer, here abbreviated as beta-layer, of lizards with hard scales and lizards with softer scales. Different antibodies for detecting Corneous Beta Proteins (CBPs) have been utilized. The agamid beta-corneous layer is generally 3–4 times thicker than in geckos, and the surface microornamentation forms a honeycomb pattern. Geckos feature thinner beta-layers and a spinulated pattern and show immunolocalization for CBPs and isopeptide bonds, a product of transglutaminase catalysis, in their thin beta-layer. CBPs and isopeptide-bonds are detected in the superficial Oberhautchen and alpha-layer of agamids while the beta-layer is immuno-negative. Considering the limitations of immunolabeling methods, the unexpected result might derive from inaccessibility of antibodies to epitopes that are masked within the packed corneous material of the agamid beta-layer. However, bioinformatics analysis for CBPs sequenced in the few species of agamids so far known indicates that these proteins have low identity with those of other lizards. This suggests that agamids possess peculiar CBPs but low isopeptide bonds in their inflexible beta-layer. In contrast, the thinner and pliable beta-corneous layers of geckos may derive from the presence of isopeptide bonds mixed with lower amounts of CBPs. The differences in material properties of lizard scales, inflexibility versus pliability, are adaptive for the different ecological conditions of the species here analyzed.</p>