Patients receiving phenytoin (PHT) may develop pseudolymphoma or, rare ly, malignant lymphoma. Previously, distinguishing the two diseases based solely on histopathology has been difficult. The recent introduction of molecular biologic techniques has provided a powerful tool to reassess this problem. A 17-year-old girl developed systemic lymphadenopathy after receiving PHT for 1 year for generalized tonic-clonic seizures (GTCS). Biopsy of a cervical lymph node showed diffuse proliferation of large lymphoid cells mimicking a large cell lymphoma. Immunophenotypic, immunoglobulin gene rearrangement, and cytogenic studies, however, showed polyclonal B-cell proliferation, consistent with PHT-induced pseudolymphoma. After PHT discontinuation, lymphadenopathy resolved in 1 month and no recurrence developed in the subsequent 10 months. Obtaining a history of drug use is crucial to recognizing this group of patients. Molecular biology and chromosome studies have become the definitive basis differentiating pseudolymphoma from malignant lymphoma in patients receiving chronic PHT therapy.