Plasma cell leukemia is a rare disease associated with very poor survival with standard treatment. We report a patient affected by plasma cell leukemia treated with aggressive chemotherapy and autologous CD34-selected PBPC who achieved a complete remission now lasting more than 2 years. Molecular studies confirmed the presence of minimal residual disease (MRD) despite the absence of disease activity. High-dose chemotherapy with stem cell rescue may be applied to selected patients considering the impact of the treatment on survival. The meaning of molecular MRD in this setting is unclear.