The activity of supported noble metal catalysts strongly depends on the particle size. The ultimate small-size limit is the single-atom catalyst (SAC), which maximizes the catalytic efficiency in the majority of the examples. Here, we investigate the catalytic behavior of Pd SACs supported on magnetite nanoparticles and we unambiguously demonstrate that Pd SACs are absolutely inactive in the hydrogenation of various alkene substrates. Instead, Pd clusters of low atomicity exhibit outstanding catalytic performance.