We report a patient with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who presented with rapid enlargement of a cervical lymph node due to localized herpes simplex lymphadenitis, which was clinically indistinguishable from large cell (Richter's) transformation. The diagnosis was made by excisional lymph node biopsy, which demonstrated CLL/SLL and zonal necrosis due to herpes simplex infection. The herpetic zone was surrounded by a brisk proliferation of immunoblasts. This case demonstrates the need for excisional biopsy and histologic examination of rapidly enlarging nodes in patients with CLL/SLL. The diagnosis of herpes simplex lymphadenitis in patients with CLL/SLL is especially important because, unlike large cell transformation, the infection usually responds well to treatment. Am.