Hydroxyapatite (Ca10(PO4)6(OH)2, or HAp) -the main mineral component of bones and teeth -is a material of great interest not only in biomedical applications but also in heterogeneous catalysis. Its framework Ca 2+ cations can be substituted by a wide variety of catalytically active metals (Cu 2+ , Ni 2+ , Ag + , etc.). In the present work, for the first time, to our knowledge, we demonstrate that highly valuable HAp-based catalysts can be obtained through a novel advantageous bottom-up approach. Unlike classical surface cation deposition in the excess of solution, this approach is one-pot. It consists in preparing the bulk-metal-substituted HAp by co-precipitation, and then submitting it to a finely adjusted thermal treatment under a H2-containing gas flow. For a Cu(~1.5wt%)-HAp, we show that such a treatment at 450 °C leads to the exsolution of the whole Cu contained in the material, leading to highly dispersed Cu species at the HAp surface. After appropriate activation, these Cu species are active in the selective catalytic reduction of NOx by NH3. The phenomenon of exsolution was reported so far mainly for perovskites, but to lead to metal nanoparticles, not to highly dispersed species as achieved here.