Enhancement of toughness is currently a critical engineering issue in tungsten metallurgy. The inherent toughness of tungsten single crystals is closely related to the capacity for local plastic slip. In this study we have investigated the plastic behavior of tungsten single crystals by means of micro-indentation experiments performed on specimens exposing (100), (110), and (111) surfaces. In parallel, FEM simulations were carried out with the Peirce-Asaro-Needleman crystal plasticity model considering both {110} aOE (c) 111 > and {112} aOE (c) 111 > slip systems. Plastic material parameters were identified by comparing the measured and predicted load-displacement curves as well as pile-up profiles. It is found that both measured and simulated plastic pile-up patterns on the indented surfaces exhibit significant anisotropy and orientation dependence, although the measured and simulated load-displacement curves manifest no such orientation dependence. The height and extension of pile-ups differ strongly as a function of surface orientation. The FEM simulations are able to reproduce the observed features of spherical indentation both qualitatively and quantitatively.