Introduction: Cases of patients with non- Hodgkin's lymphoma observed after therapy for Hodgkin lymphoma have been reported. However, occurrence of non-Hodgkin's lymphomas in such settings at a previously uninvolved site is extremely rare. The mechanism behind this remains obscure thereby presenting diagnostic and therapeutic dilemma for the treating physician. Case Report: We report a case of a 62-year-old woman who developed a large B-cell non-Hodgkin's lymphoma at a different anatomic site six months after receiving high dose chemotherapy and autologous stem cell transplantation for her relapsed Hodgkin lymphoma. We treated her with conventional combination chemoimmunotherapy following which she achieved durable complete remission. Conclusion: This case highlights the intriguing relationship between classical Hodgkin lymphoma and B-cell non-Hodgkin's lymphoma with respect to pathogenesis and its impact on therapeutic decisions and outcomes in such contentious cases which a clinician must face.