This chapter addresses myelodysplastic syndromes (MDS), a heterogeneous group of clonal stem cell diseases characterized by peripheral cytopenias, ineffective hematopoiesis, and dysplasia in one or more major myeloid cell lines. The diagnosis is often straightforward but can also be difficult in cases in which some cardinal features are lacking. High-quality preparations are needed for accurate assessment of dysplasia, but the assessment of the degree of dysplasia is hampered by various factors. Although many molecular abnormalities have recently been identified in MDS patients, their diagnostic and prognostic utility have not been determined. In addition, clinicians and hematopathologists should consider copper deficiency in patients misdiagnosed with MDS, including patients who have been given the diagnosis of low-risk MDS (without increased blasts) and a normal karyotype. This chapter presents six cases that illustrate some of the complexities we have encountered in the clinic and our diagnostic approach.