Homogeneous (Cu2+ ions) and heterogeneous (Cu2+-pillared clay) Fenton-like catalysts have been compared in the conversion of p-coumaric acid. The performances of the two classes of catalysts are similar for an analogous amount of copper, but there are some relevant differences in terms of (i) the presence of an induction time, (ii) the turnover frequency, (iii) the efficiency in the use of H2O2, (iv) the initial attack of p-coumaric acid (hydroxylation on the aromatic ring or oxidative attack on the double bond of the lateral chain), and (v) the effect of dissolved oxygen on the removal of total organic carbon (TOC). These differences were interpreted in terms of reaction network of generation of radical oxygen species and of organics conversion. The possible formation of a surface peroxo adduct coordinated to a copper binulcear site was also evidenced for the solid heterogeneous catalyst.