Primary myelodysplastic syndromes (MDS) occur in the absence of exposure to ionizing radiation, chemotherapeutic agents or myelotoxic drugs, whereas secondary MDS occurs in the presence of such exposure. We encountered 4 patients among 217 patients on hydroxychloroquine for rheumatological conditions in 2005 diagnosed with MDS. Two patients were male and two were female; the median age was 69.75 years, (range 65-76). The dose of hydroxychloroquine for all patients was 400 mg daily with median treatment duration of 10.5 years and a range of 6-16. All patients had bone marrow biopsy confirmation of the diagnosis of MDS. The incidence of MDS in a group older than 70 years ranges from 15 to 50/100,000 persons per year. The diagnosis of 4 cases of MDS among 217 patients in 1 year is approximately 123-137-fold higher than the risk of MDS in the general population aged more than 70 years (P < 0.001) and suggests that long-term treatment with hydroxychloroquine is associated with an increased risk of developing secondary MDS.