Thermodesorption of cadmium arachidate multilayers is studied by optical surface analysis and by mass spectrometry measurements. The optical reflection technique has been improved to discriminate signal contributions from desorption and light scattering. The scattering arises from film heterogeneities that are also observed by Nomarsky microscopy. The assessment of these heterogeneities is important to understand mass spectrometry data. Both the optical technique and mass spectrometry are sensitive to observing the multilayer phase transition at 110 °C and the desorption near 200 °C (at the heating rate applied). The mass spectrometry analysis yields detailed information on the desorbing species and hence on the desorption mechanism, whereas the optical reflection technique, because of its ease of application, can be used for screening materials and processes. In addition, it can be used to calibrate the mass spectrometry signal as a rate of thickness changes.