A Co-59 solid-state NMR study of a single crystal of vitamin B-12 was performed at 11.75 T. The results showed that the cobalt nucleus in this biologically relevant molecule experiences a highly anisotropic chemical shift spanning 1200 ppm about the isotropic chemical shift of 4549 ppm. The large electric field gradient of the cobalt site results in a quadrupolar coupling constant of 27.31 MHz with asymmetry of 0.243. The two tensors describing the orientation dependence of these NMR interactions exhibit distinct orientations with respect to the molecule, the quadrupolar coupling lying close to the axial direction, and the chemical shift tensor tilted 41 degrees away from this direction. This study demonstrates the importance and feasibility of single-crystal NMR to provide this orientation information in metal-centered biological assemblies, and supports the prospects for solid-state NMR of quadrupolar metal nuclei to contribute further to the elucidation of metal participation in biological systems.