Mo/Al2O3 and Mo/ZrO2-Y2O3 catalysts sulfided at different temperatures were tested in thiophene hydrodesulfurization (HDS) and examined by high resolution electron microscopy (HERM). Higher activities observed for the Mo/ZrO2-Y2O3 sample appear to be correlated to a lower stacking of the layers in the MoS2 Crystallites, solely the top edge sites being catalytically active. Moreover the results suggest that a dual vacancy site is required for the thiophene HDS.