Rituximab (the chimeric anti-CD20 antibody) is widely used in the treatment of CD20 positive non-Hodgkin's lymphoma (NHL). The response rate at relapse after repeated use in prior CD20 positive responders is lower than 50%. Several mechanisms can be responsible for rituximab resistance. CD20 negative relapses which transformed from CD20 positive aggressive and indolent forms of lymphoma can be the one of the reason of secondary resistance to rituximab. The authors report a case with combination of aggressive and indolent form of lymphoma who relapsed after 7 months from the last dose of rituximab therapy. CD20 transformed negative from positive in her relapsed disease. Patients with CD20 positive B cell NHL must rebiopsy after first line rituximab therapy if their disease relapsed or progressed.