The attenuation length approach for determination of an overlayer thickness is analyzed in the case of overlayer/substrate systems in which both materials distinctly differ; in particular, they exhibit considerably different electron transport properties. Typical measurement conditions for overlayer-thickness determination were simulated for numerous systems using an advanced Monte Carlo strategy. Three experimental procedures were considered: (i) measurement of only one signal intensity from an overlayer; (ii) only one signal intensity from a substrate; and (iii) measurement of two signal intensities from an overlayer and a substrate. It turned out that differences in electron transport properties of the overlayer and substrate materials (elastic scattering cross sections, the inelastic mean free path) can generally be ignored. One can safely assume that the overlayer and substrate materials are identical, and the effective attenuation length (EAL) values needed in calculations should correspond to the overlayer material only. Furthermore, one can use for that purpose the EALs estimated for the overlayer material from available predictive formulas. However, care must be taken to estimate correctly the needed albedo values. In that case, the overlayer thicknesses assumed in Monte Carlo simulations are reproduced from calculated signal intensities within 2 – 3%.