The goal of the current study is to evaluate the role of beta-catenin in chronic myeloproliferative disorders. Expression of beta-catenin was analyzed by immunohistochemistry in formalin-fixed decalcified bone marrow biopsy specimens from 52 chronic myeloproliferative disorder cases and 6 nonchronic myeloproliferative disorder bone marrows as controls. The frequency of moderate to strong beta-catenin staining of megakaryocytes was significantly higher in polycythemia vera cases and in essential thrombocythemia cases than in chronic myelogenous leukemia cases (polycythemia vera versus chronic myelogenous leukemia, P = .002345, Fisher exact; and essential thrombocythemia versus chronic myelogenous leukemia, P = .002288), chronic idiopathic myelofibrosis cases (polycythemia vera versus chronic idiopathic myelofibrosis, P = .006707 and essential thrombocythemia versus chronic idiopathic myelofibrosis, P = .006932) or control cases (polycythemia vera versus control, P = .010489 and essential thrombocythemia versus control, P = .0113120). The erythroid and myeloid lineages showed absent to weak beta-catenin staining in most cases. In conclusion, these results indicate that the Wnt/beta-catenin signaling pathway may have a role in megakaryocytopoiesis in polycythemia vera and essential thrombocythemia. In addition, beta-catenin may be a useful marker for differentiating polycythemia vera and essential thrombocythemia from other types of chronic myeloproliferative disorders.