Most animal chemical signals comprise a complex mixture of compounds, each with its own chemical properties, which are combined to maximize signal efficacy in a given environment. Such blends forms integrated functional units hypothesized to be shaped by selective forces acting on the functional mixture as a whole, rather than on a single component. Chemical communication plays a pivotal role in lizards, and many species have developed specialized epidermal glands whose secretions are waxy, homogeneous blends of lipids and proteins used for intra- and inter-specific signalling. Lipids are historically considered the main semiochemical source, while proteins provide mere structural support to the lipophilic fraction. Recent discoveries, however, point towards a key signalling role for proteins, as well. The potential signalling functions of both proteins and lipids let use to hypothesise that they should undergo to a certain degree of integration. We tested this hypothesis by comparing the composition and complexity of the lipophilic and proteinaceous fractions of the epidermal gland secretions of 36 lizard species (Lacertidae), and combining quantitative, phylogenetically-informed analysis with tandem mass spectrometry to identify the proteins responsible for such a potential association. We found the composition and complexity of proteins and lipids to be strongly correlated. Protein composition was mostly influenced by the relative proportion of cholestanol, provitamin D3, stigmasterol, and tocopherol, while the complexity of the protein pattern increased with that of lipids. Additionally, two identified proteins (carbonic anhydrase and protein disulfide isomerase) increased their concentration as provitamin D3 became more abundant. Our results validate the hypothesis of an integration between the lipid and protein fractions of lizard secretions. The prevalence of proteins with enzymatic properties suggests the integration to be more complex than previously thought: proteins may serve to modulate the efficacy, stability, and durability of the signal, by dynamically controlling the chemical environment of the blend. Likewise, we cannot exclude that proteins contribute to the semiochemical function of the mixture, maybe forming with lipids an individual-specific chemical profile. Here we present the original data not available from other, already published researches (i.e., protein electrophoretic profiles and lipid composition). Notably: LM8.xls = excel sheet reporting the percentage concentrations of the eight lipids specifically used to characterize the lipophilic fraction MSdata.zip = mass spectrometry raw files (in .mzXML format) obtained from the analysis of the three molecular weight region related to the increase in provitamin D3 abundance.