Primary care physicians (PCPs) may lack a basic understanding of myelodysplastic syndromes (MDS). Two case studies, presented to 44 internal medicine residents and outpatient attending internists, highlighted a potential knowledge gap. A differential diagnosis of MDS was overlooked in a 72-year-old man with several comorbidities and a hemoglobin level of 9.2 g/dL (historical levels, 10.8 to 11.2 g/dL). Despite the acute change in hemoglobin levels, and the presence of comorbid lung and heart disease, there was no immediate recommendation from the PCPs for specialist referral. In contrast, in the second case study a 76-year-old man with a 6-month history of recurrent infections, fatigue, a hemoglobin level of 7.2 g/dL, and multilineage cytopenias typifying the clinical presentation of MDS did receive further attention and workup. With these cases as background, this article examines the potential reasons for the failure of many PCPs to identify MDS, and suggests steps to be taken to improve its diagnosis, early referral, and treatment.