We developed an advanced method for producing undiluted nano-particulate pressed powder tablets without addition of any binder applying wet-milling protocols in aqueous suspension using a high power planetary ball mill and agate tools. The method was tested and optimized for the milling time, ball size, ball-to-powder ratio and water-to-powder ratio using pulverized diorite DR-N containing abundant zircon crystals that are especially difficult to break down by both milling and acid-digestion methods. The new method produces nano-particulate powders with typical grain size d₅₀ < 1.5 μm allowing us to form pressed powder tablets with excellent cohesion and homogeneity suitable for laser ablation micro-analysis. The optimized milling protocol was applied to a selection of other natural rock CRMs (BHVO-2, JGb-1, UB-N, AC-E, GA) covering a wide range of rock types, and formed powder tablets were analyzed by LA-ICPMS. Precision was found to be in the same range of <2–5%RSD as it is obtained from laser ablation analysis of glasses (e.g., volcanic glasses, vitrified rock powders), and preferred values could be reproduced within uncertainty for most of the 38 trace and ultra-trace elements analyzed. Our new method accomplishes the preparation of refractory sample materials or materials containing refractory mineral phases (e.g., plutonic rocks and sediments, ultramafic rocks, oxides as in banded iron formation, ceramics) for subsequent analysis by LA-ICPMS. Even more importantly, this method opens up new prospects for the manufacturing (and possibly isotopic spiking) of homogenized reference materials from natural minerals that are urgently needed for true matrix-matched calibration and validation of LA-ICP-MS geochemical and isotope data.