AbstractEvolution of low‐grade Non‐Hodgkin Lymphoma (NHL) into a more aggressive neoplasm is a common, well‐documented event in NHL. The reverse process, in which a less aggressive component becomes evident during the course of treatment for a highergrade NHL, has only recently been recognized. This lymphoma “downgrading” has been reported at the time of relapse in both radiation‐ and chemotherapy‐treated patients who initially presented with high‐ or intermediate‐grade lymphoma. The etiology of this unusual transformation has not yet been determined. We present the clinical, morphologic, immunologic, and flow‐cytometric features of a patient with diffuse immunoblastic lymphoma who achieved a complete response to chemotherapy and then relapsed with follicular small‐cleaved‐cell lymphoma 3 years later. Morphologic and immunophenotypic findings suggest that both immunoblasts and small cleaved cells were present in the initial biopsy. DNA content analysis of the initial and relapse biopsies suggests that the immunoblastic component was more susceptible than the small cleaved cells to the chemotherapy that the patient received. Successful eradication of the rapidly proliferating immunoblasts with survival of less rapidly proliferating small cleaved cells may account for the unusual histologic transform