Conventional methods to analyze biochemical processes related to contaminant toxicity usually require the sacrifice of animals to collect tissues and organs. However, for ethical reasons and especially for endangered species, non- or minimal-invasive methods should be preferred. Among vertebrates, reptiles show a general decline worldwide and therefore the use of non- or minimal-invasive methods to measure some biochemical processes in these animals are encouraged. It is well known that most lizards use a common safety behavior implying the natural loss of tail in the case of predation events. Therefore, if common analyses testing contaminant toxicity could be performed in tail tissue, this method, not implying the sacrifice of the animals, could be considered as a good minimal-invasive method. The aim of this study is to test on wild Italian wall lizard Podarcis siculus the use of tail to detect a large set of biomarkers including oxidative stress (TOSCAROO, TOSCAOH, CAT, tGSH, MDA), biotransformation processes (EROD, GSTs) and neurotoxicity (AChE, BChE). All the biochemical responses, excluding EROD and MDA, resulted to be analytically detectable in tail tissues of P. siculus, although the mean values obtained with this minimal-invasive method were significantly lower than those obtained with invasive one.