Turquoise is a well-known gemstone that has been used in artefacts across many cultures throughout history. However, due to its porosity it is often treated to enhance its color and beauty. One appreciated treatment is the patented Zachery process, although its details remain publicly undisclosed. Previous studies indicated that only a high K content distinguishes Zachery-treated from natural turquoises. In this study, natural and Zachery-treated turquoise samples from the famous Kingman mine, Arizona, USA, were analysed by means a multi-methodological approach, including standard gemological testing, electron microprobe (EMPA), scanning electron microscope with energy dispersive spectrometer (SEM–EDS) and X-ray diffraction (XRD), Fourier-Transform InfraRed (FTIR), non-destructive External Reflection-Fourier-Transform InfraRed (ER-FTIR) spectroscopy and X-ray computed microtomography (μCT). The results revealed new chemical–mineralogical and microstructural features that distinguish the Zackery-treated from the natural turquoise: higher specific gravity and lower porosity, associated with high and uneven concentrations of Cu, K and Na, the occurrence of tenorite (CuO), the presence and extension of reaction edges in the entire volume are distinctive of treated samples. Moreover, Cu-rich seeds and feldspar crystals may be interpreted as additional components used during the treatment. The hypothesis is that the Zachery treatment induces the re-crystallization of a new turquoise-like phase, which differs from the natural one from a chemical and microstructural point of view.