Predicting the hydrotreating performance of industrial catalysts used for upgrading heavy oils is hampered by the unknown chemistry behind it. In this work, we have used a set of chromatographic and mass spectrometric techniques (APPI/ESI FT-ICR MS, FID-MS GC × GC and PFPD GC) for acquiring a more precise composition of the feed and products of the hydrotreatment of a blend of light cycle oil and scrap tire oil (20 vol%) using three benchmark catalysts: CoMo/Al2O3, NiMo/SiO2-Al2O3 and NiW/USY zeolite. Despite the different nature of the catalysts, the composition of the products was relatively similar, indicating the slower and controlled transformation of the heaviest molecules of the feed, particularly in tire oil. A faithful analysis of these molecules by combining the results of the analysis clarifies the multiple mechanisms affecting hydrotreating simultaneously: hydrodearomatization, hydrocracking, hydrodesulfurization, hydrodeoxygenation and hydrodenitrification. An effort has been made to use these results in a quantitative manner for catalyst screening.