We have recently developed a novel mouse model for studying the infiltration of malignant lymphoma to the eye and brain. After i.p. inoculation of variant S49 mouse lymphoma cells into young mice (optimum: day 7 postnatal), specific homing of these cells (named Rev-2-T-6) to the brain and eyes took place. This model offers an opportunity to study the routes of infiltration to these sites and spread thereof, as well as the molecular mechanisms that govern this metastasis. By applying a time course histopathological analysis, we demonstrate that infiltration of the brain and eyes can be visualized as early as days 9 and 14 after inoculation, respectively. The lymphoma cells enter the brain preferentially through the choroid plexus and cranial nerves. Infiltration of the rostral part occurs before the caudal part of the brain. Once within the brain, the cells spread within it as well as migrate along the optic nerve sheath into the eyes, where they continue to migrate along the choroid, ciliary body, iris, and into the anterior chamber of the eye. The orbit is also infiltrated by the lymphoma cells. However, this occurs independent of the brain-optic nerve-intraocular route.