Myelofibrosis with myeloid metaplasia (MMM) is an infrequent disease usually affecting elderly people. Due to the lack of a specific marker for MMM, efforts are being made to refine the diagnostic criteria. A prefibrotic form of the disease has recently been recognized and a set of diagnostic criteria proposed by the Italian Consensus Conference for the Diagnostic Criteria of MMM. Moreover, the number of circulating CD34(+) cells has recently been proven to be useful in the differential diagnosis of the disease. Median survival of patients with MMM is about 5 years, but there is wide variability. Hemoglobin level at diagnosis is the most important prognostic factor, whereas age, constitutional symptoms, low or high leukocyte counts, blood blast cells, cytogenetic abnormalities, and number of circulating CD34(+) cells are also of prognostic value. Based on some of the above factors, several prognostic systems of MMM have been proposed to identify at presentation subgroups of patients with a different risk profile. This is especially important in younger individuals, who may benefit from therapies that have curative potential but also involve a mortality risk (notably, allogeneic hemopoietic stem cell transplantation). Since no disease-oriented therapies for MMM are currently available and treatment is based on palliation and improvement of quality of life, therapy should be formulated according to the form of presentation of the disease and its prognostic implications. A staging system for MMM that meets treatment requirements and available therapeutic resources should be developed by considering parameters able to predict not only survival but also other disease outcomes, such as development of anemia, thrombocytopenia, splenomegaly, and blast transformation. Such a staging system should be derived from a large population of patients, systematically collected from diagnosis without selection bias and followed over time.