Thorough investigation of the stages preceding the diagnosis of overt MPN, similar, for instance, to the studies that established monoclonal gammopathy of undetermined significance (MGUS) as the precancerous stage of multiple myeloma, is needed in MPNs to validate the hypothesis of chronic (antigen-mediated or not) stimulation of myelopoiesis preceding the acquisition of JAK2, MPL, or CALR mutation. The gene discussed is CALR; the disease is myeloproliferative neoplasm.