Dameshek first postulated a common myeloproliferative heritage for the myeloproliferative disorders, now termed neoplasms. This prescient observation was validated by the description of a common mutation in exon 14 of JAK2 for patients with essential thrombocythemia, polycythemia vera and primary myelofibrosis. In recent years, our knowledge of the molecular abnormalities underpinning these disorders has expanded significantly. At the same time, we have continued to use a classification based largely upon the first clinical descriptions of these entities, which sometimes proves problematic in differentiating between these conditions and normal reactive processes, myelodysplasia and between the myeloproliferative neoplasm entities themselves. Here, we discuss the pros and cons of a molecular classification and its potential utility in diagnosis, prognosis, and therapeutics.