The European Myelofibrosis Network (EUMNET), a European research network on myelofibrosis with myeloid metaplasia (MMM), has developed a definition of response for the disease by using clinicohematologic, histologic, and cytogenetic criteria. A core set of 5 clinicohematologic criteria was selected out of 9 candidates on the basis of their sensitivity to change measured in 196 patients treated either during clinical trials or routine clinical practice. A consensus panel of 16 international experts was convened and asked to score the level of response in 104 patient profiles as major, moderate, minor, or no response according to changes of the clinicohematologic criteria. Using the experts' consensus as the gold standard, the performance of 100 possible definitions of response was evaluated. Criteria for major or moderate clinicohematologic response were determined to be changes in hemoglobin (Hb) and spleen size and the presence of constitutional symptoms, while changes in platelet count and white blood cell (WBC) count served as complementary criteria and were of value for defining minor responses. A histologic response was defined by changes in bone marrow fibrosis and cellularity grades. The combined use of these response definitions should help standardize the design and reporting of future clinical studies in MMM.