The Hematology Disease Site Group of the Cancer Care Ontario Practice Guidelines Initiative has systematically reviewed the published literature and, through a consensus process, developed an evidence-based practice guideline assessing the role of stem-cell transplantation in patients with multiple myeloma. The conclusions were validated by solicited feedback from 221 practitioners across Ontario, Canada. The guideline comprises six recommendations: 1) Autologous transplantation is recommended for patients with stage II or III myeloma and good performance status. Evidence of benefit is strongest for patients who are younger than 55 years of age and have a serum creatinine level less than 150 micromol/L (<1.7 mg/dL). Physicians must use clinical judgment in recommending transplantation to other patients. 2) Allogeneic transplantation is not recommended as routine therapy. 3) Patients potentially eligible for transplantation should be referred for assessment early after diagnosis and should not be extensively exposed to alkylating agents before collection of stem cells. 4) Autologous peripheral blood stem cells should be harvested early in the patient's treatment course. The best available data suggest that transplantation is most advantageous when performed as part of initial therapy. 5) The comparative data addressing the specifics of the transplantation process are insufficient to allow definitive recommendations. In the absence of such data, a single transplant with high-dose melphalan, with or without total-body irradiation, is suggested for patients undergoing transplantation outside a clinical trial. 6) At this time, no conclusions can be reached about the role of interferon therapy after transplantation.