Neuropathological and radiographical findings of two patients with primary CNS B cell lymphoma are presented. Prior to computerized tomographic (CT)-guided stereotactic biopsy both patients had received glucocorticoid therapy which led to marked tumor regression on CT scans and transient improvement of neurological deficits. Despite careful targeting and serial sampling, multiple biopsy specimens examined cytologically, histologically and immunomorphologically showed nonspecific reactive astrogliosis and conspicuous perivascular infiltrates of T lymphocytes. A second biopsy performed after an interval of 2 and 8 weeks, respectively, and short-term discontinuation of dexamethasone therapy in one case, unequivocally established the diagnosis of Non-Hodgkin lymphoma. It is concluded that steroid therapy may obscure the bioptic diagnosis of cerebral lymphoma. In addition to the well-known antiedematous effect of glucocorticoids neuropathologists and neurosurgeons should be aware of a rapid and pronounced lymphodepletive action of steroids on malignant CNS lymphomas.