The role of water, vapor or layer adsorbed on the solid surface, in the spreading of molecular films is not fully recognized at the present time. The aim of this paper is to provide examples of the influence of water on the thickness profiles of spreading microdroplets, recorded using spatially resolved ellipsometry. The analysis of experimental data is done in reference to a recent theory of de Gennes (de Gennes, P. G.; Cazabat, A. M. C. R. Acad. Sci., Ser. II 1990, 310, 1601) on the spontaneous spreading of incompressible, nonvolatile liquids. A tentative discussion on the role of water on molecular friction, local chemical potential in the film, or solid-liquid interaction energies is presented.