In an effort to better understand, direct and control the crystallization of molecular and macromolecular compounds, an approach using colloidal templates as substrates for heterogeneous nucleation was investigated. These templates combine both tuneable chemical functionalities and geometrical features, altering the crystal-substrate interactions. Colloidal templates were prepared from silica nanoparticles, where the surface chemistry was modified by silanization. Particle size varied from 30 to 700 nm, with silanols, NH(2), CF(3), phenyl, or dodecyl as surface functional groups. Here, we report on the template assisted crystallization of chicken egg white lysozyme (CEWL). Nucleation was dramatically affected by the surface chemistry and topography of the templates. Using 220 nm particles, hydrophobic templates generally produced fewer, larger crystals, while a larger number of small crystals were obtained on hydrophilic templates. The use of different particle sizes also affected the crystal size, the optimal for nucleation being 432 nm. Classical Nucleation Theory (CNT) can interpret surface chemistry effects but does not support the effect of particle size. This paper reports that the combined use of both geometrical and chemical interactions results in an increased ability to control the nucleation and growth of protein crystals.