Patients referred to tertiary care centers occasionally may have their diagnostic procedures repeated and have a final diagnosis that differs from that of the referring center. The aim of this study was to evaluate discordance rates and their clinical implications in the diagnosis of patients with myelodysplastic syndrome (MDS) referred to a tertiary center. We analyzed 915 patients with MDS who were referred to M. D. Anderson Cancer Center between September 2005 and December 2009. Discordance in the diagnosis was documented in 109 (12%) patients, with a majority reclassified as having higher-risk disease by French-American-British (67%) or by International Prognostic Scoring System (77%) with implications for therapy selection and prognosis calculation. These results demonstrate the complexity of the diagnosis of MDS and highlight the need for confirmation of diagnosis when in doubt.