Studies performed on mice and healthy human volunteers have shown that a single dose of pegfilgrastim (Peg-GCSF) is effective in stimulating peripheral blood stem cells (PBSC) mobilization. This prompted us to try the stimulation with pegfilgrastim in a patient previously non-mobilizing with a combination of chemotherapy and filgrastim. In December 2003, a 65-yr-old man was diagnosed as having stage III A IgG/k multiple myeloma. He received three courses of polichemotherapy (DC-IE) obtaining a stable response. Afterwards, the patient was treated with high-dose cyclophosphamide (CPM; 7 g/sqm) plus daily 10 mcg/kg filgrastim in order to mobilize PBSC, without success. After 2 months off therapy, the disease progressed and the patient received alternate cycles VAD (vincristine, dexamethasone, adriblastine)/high-dose dexamethasone. A second attempt to mobilize PBSC, using daily 10 mcg/kg filgrastim after the second and third VAD cycle, failed. In a further attempt to mobilize PBSC, we administered a single dose of 12 mg pegfilgrastim on day 5 after a fourth VAD course. Daily evaluation of circulatory CD34+ cells was started from day 8 after the end of chemotherapy. On day +10 postchemotherapy the CD34+ cell count was 24/μL and two aphaeresis were performed, harvesting 1.6 × 106 and 0.89 × 106 CD34+ cells/kg respectively (total 2.49 × 106 cells/kg). The only side effect was moderate skeletal pain. The patient underwent successful transplantation. The median times necessary to recover 0.5 × 109 PMN/L and 20 × 109 platelets/L after PBSC reinfusion were 9 and 12 d respectively. The patient did not need red blood cell or platelet transfusions. He experienced a sustained engraftment and maintains complete remission 9 months after the reinfusion. In conclusion, a single dose of pegfilgrastim was able to mobilize a sufficient number of CD34+ in a multiple myeloma patient not responsive to two previous attempts with high or standard dose chemotherapy followed by filgrastim. This approach, if confirmed on larger series and other diseases, could open new opportunities in stem cell mobilization for poor or non-mobilizers.