Primary lymphoma of the central nervous system is an uncommon neoplasm that requires definitive diagnosis because it is potentially treatable. We report a case in which the diagnosis of lymphoma was unsuspected and was made by needle biopsy with computed tomographic scan direction. A frozen section immunoperoxidase technique demonstrated monoclonality. When combined with a compatible morphological appearance, this confirmed the diagnosis of lymphoma. This case demonstrates the importance of this immunochemical method in the rapid diagnosis of central nervous system lymphomas.