The thermal spreading of MoO3 onto silica was studied in comparison with the thermal spreading onto alumina using different characterization techniques. X-ray diffraction results showed that MoO3 crystals were transformed into Mo amorphous species on alumina and silica supports by thermal treatment. Laser Raman spectroscopy results also evidenced the transformation of MoO3 bulk into small Mo clusters and/or dispersed Mo species, which are highly distorted, interacting with alumina and silica supports, X-ray photoelectron spectroscopy and diffuse reflection spectroscopy (DRS) results gave better evidence of the presence of higher amounts of Mo species at the surface of both supports when compared with the respective physical mixtures. Fourier transform infrared spectroscopy also provided good evidence that a surface reaction may have occurred between MoO3 and hydroxyl groups on both supports. It was possible to infer that the original MoO3 crystal lattices were destroyed by reacting with the support surface as a result of thermal treatment and transformed into small Mo clusters, dispersed Mo species, or both. Moreover, Raman spectroscopy showed nicely that the interaction of Mo species was higher on alumina than silica surfaces, Raman and DRS also provide insight into Mo species dispersion on alumina and silica samples, whereas DRS provided better evidence of the presence of dispersed Mo species on these supports. It was possible to infer that all calcined physical mixtures exhibited dispersed Mo species and small Mo clusters together with a small quantity of bulk MoO3 that remained after thermal treatment. Therefore, similar results obtained on both supports demonstrated that the thermal spreading of MoO3 also occurred on silica and the same mechanism was observed as on alumina. However, the Mo dispersion and some Mo species were different on the supports that call be attributed to the different surface properties of silica and alumina.