BACKGROUND Spontaneous regression of non-Hodgkin's lymphoma, occasionally reported in low grade groups, is a rare phenomenon in high grade groups. Clonal proliferation has not been confirmed in the majority of reported cases. In this woman, age 58 years, who had been diagnosed as having high grade immunoblastic lymphoma after excision of a single cervical lymph node, the remaining bilateral cervical, inguinal, and axillary adenopathy regressed completely without any cytotoxic treatments 22 days after biopsy. At the time of this writing, the patient has been free of disease for 24 months. METHODS Clonality of the lymphoproliferation in the case was examined by immunohistochemistry and polymerase chain reaction (PCR) amplification using paraffin embedded biopsy material. Possible implications of Epstein-Barr virus in the pathogenesis of this process was examined also by PCR amplification and in situ hybridization. RESULTS The proliferating lymphoid cells showed restricted expression of immunoglobulin (Ig) light chain and amplification of clonally rearranged V-D-J regions of Ig heavy chain gene. Epstein-Barr virus did not appear to be involved in the process. CONCLUSIONS The present study shows that spontaneous complete regression of clonal lymphoproliferation that is morphologically a high grade lymphoma can occur.