The use of chemotherapy and/or haematopoietic growth factor-mobilized peripheral blood stem cells (PBSC) has been shown to induce a more rapid haematopoietic recovery than the reinfusion of bone marrow (BM)-derived haematopoietic cells, thus reducing the morbidity and mortality of autologous stem cell transplantation (ASCT). PBSC collections were initially believed to have a lower incidence of tumour cells involvement than BM harvests. However, recent studies have shown that mobilized blood cell products of cancer patients eligible for autografting are frequently contaminated with tumour cells. Whereas positive selection of haematopoietic CD34+ stem cells has been largely used as a means of indirect purging of circulating CD34+ neoplastic cells, few groups have addressed the issue of tumour cell removal by direct targeting of cancer cells using physical or pharmacological strategies. In this chapter we review the available data concerning the contamination of tumour cells in PBSC collections from cancer patients, the functional and kinetic characteristics of primed CD34+ cells which may affect the haematopoietic toxicity of purging procedures developed to eliminate the minimal residual disease (MRD) from BM samples, and the preclinical and clinical results of the selective killing of residual tumour cells from leukaphereses. The limited amount of data published so far do not allow any firm conclusion on the clinical usefulness of purging protocols. Nonetheless, the successful extension of ex vivo purging to PBSC collections may improve the feasibility of randomized studies aimed at determining the importance of tumour-free autografts.