Iron overload (IO) is associated with free radical generation and tissue damage. Our main objective was to ascertain if very high levels (VHL) of ferritin (>/=3000 microg/l) and transferrin saturation (TS) >/=100% during conditioning had an impact on overall survival (OS) and transplant-related mortality (TRM) after a haematopoietic stem cell transplantation (HSCT). Levels of ferritin and TS were measured at days -7 and -4, respectively, in 25 patients who underwent HSCT after CY/TBI. The group consisted of 20 men and five women with a median age of 40 years. Fifteen patients were autotransplanted and 10 allotransplanted. Nine of them had a diagnosis of AL, six of CML and 10 of lymphoma. Thirteen of them were in early and 12 in advanced status of disease. VHL of ferritin and TS >/=100% were associated with a decreased OS (P = 0.001 and P = 0.006, respectively) and an increased TRM (P = 0.003 and P = 0.004, respectively) in univariate survival analysis. Both variables remained significant at multivariate analysis for OS (P = 0.03 and 0.02, respectively) and TS was an independent factor for TRM (P = 0.01). Ferritin was very close to achieving statistical significance for TRM (P = 0.06) in multivariate analysis. In conclusion, VHL of ferritin and TS >/=100% at conditioning are associated with an increase in toxic deaths after transplant.