In order to develop methods to determine the chemical composition of Waste Printed Circuit Boards (WPCB), this study focused on the analysis of 10 metals (Cu, Fe, Sn, Zn, Pb, Ni, Sb, Cr, Mo and Pd) using portable X-ray fluorescence (pXRF) compared to ICP-MS measurements after aqua regia digestion. Different experimental conditions were tested: 3 particle sizes (200 µm, 750 µm and 2 mm) and 3 sample preparations (tube, cup and loose powder). For each condition tested, 8–16 independent replicates were done. ICP measurements with the 200 µm sample, considered as the reference condition in this study, confirmed the homogeneity of the sample at this particle size and the robustness of the sampling protocol (RSD < 5% for all elements). For this particle size, pXRF has low data dispersion too (Cu, Fe, Sn, Zn, Pb, Sb and Cr showed RSD < 10%) and the use of loose powder seems to be a sufficient preparatory step. Moreover, the deviation of pXRF measurements with the 200 µm sample from the reference condition was acceptable (<20%) for Cu, Sn, Zn, Pb, Ni, Sb and Mo. For coarser samples, i.e. 750 µm and 2 mm, the homogeneity was much more doubtful, which needs to be offset by a larger number of repetitions. For these particles sizes, pXRF set to factory-installed mining mode did not produce accurate measurements but could provide a rapid non-intrusive approach for first-level screening to assess the relative difference of metal contents between WPCB samples.