Because of increasing popularity of tattoos throughout society, it is important to improve tattoo safety and to gather information if and how the colour-giving tattoo pigments react in the human body. Tattoo inks are a suspension of insoluble inorganic or organic pigments in a solvent, such as primary alcohols, glycols or water. Binders or thickening agents stabilize the pigments in the suspension. During tattooing, the ink is applied into the upper part of the dermis of the skin. It is known that there are adverse skin reactions in tattooed skin like allergic and inflammatory reactions. Due to the unique exposure pathway, inaccurate labelling and the lack of appropriate patch test preparations, it is difficult to identify the substances causing the adverse reaction. Tattoo inks often contain several substances. Some of them are not even identified, because the used pigments are not produced for tattooing and only have a purity of 70–90 %. Some pigments themselves, organic impurities, metals, photochemical degradation products and also metabolites of the pigments are discussed as culprit sensitizers. To understand the cause of adverse skin reactions, in particular contact allergies, in tattooed skin, it is important to identify the organic and inorganic pigments as well as other metals in skin biopsies in various skin samples. Laser ablation (LA)-based bioimaging with simultaneous elemental and molecular mass spectrometry (MS) enables a fast and easy way to find out about the spatially resolved distribution of pigments and metals in skin biopsies with adverse reactions. For this purpose, a LA system is hyphenated via splitted transfer lines with an inductively coupled plasma (ICP)-MS for elemental analysis and with an atmospheric pressure chemical ionization (APCI)-Time-of-Flight (ToF)-MS for molecular analysis. By simultaneously hyphenating LA with ICP-MS and APCI-MS, different metals, inorganic and organic pigments have been successfully identified in skin biopsies with adverse reactions. It was shown that LA-ICP-MS/APCI-MS provides a fast and easy way to generate spatially resolved bioimages of endogenic elements, organic and inorganic pigments as well as other metals in human skin samples to learn more about possible triggers of adverse reactions in tattooed skin. The distribution of the identified substances in the analysed skin samples matched very well and could be clearly assigned to the tattoo. This information may help to understand the cause of the present adverse skin reactions and allergic skin reactions caused by tattoos in general.