The main objective of the study was to analyze the incidence of iron overload (IO) and its management in transfusion-dependent patients with low-risk myelodysplastic syndrome (MDS) before the license of deferasirox. This observational, cross-sectional, and multicenter study was conducted from January to May 2007 in 81 Spanish hospitals. Eligible patients had a low or intermediate-1 risk score and had to have received at least ten units of packed red blood cell (PRBC). Of the 549 patients analyzed, 75% had received more than 20 PRBC units since diagnosis; 14% had IO at diagnosis and 58% at last follow-up. Thirty-eight percent of patients received chelation therapy; of those, 92% were treated with desferrioxamine. Ferritin levels at the start of chelation therapy were higher than 1,000 microg/L in 76% and over 2,500 microg/L in 24% of patients. Of the 202 patients who received some form of chelation therapy, ferritin levels increased from a mean +/- SD of 1,986 +/- 1,398 to 2,480 +/- 1,648 microg/L at last follow-up in 86% (p < 0.001). In the remaining 29 patients treated with a minimally effective therapy, ferritin levels did not increase. Of these, only 11 patients received such therapy lasting more than 12 months. In conclusion, most low-risk transfusion-dependent MDS patients develop IO, but only a minority receives a minimally effective and timely iron chelation therapy.