Mutations within the myeloproliferative leukemia virus (MPL) gene have been identified in some myeloid neoplasms; however, myeloid neoplasms with MPL mutations (MPL+) have not been well characterized. This study investigated the disease distribution, morphology, cytogenetic abnormalities, and select clinical features of MPL+ myeloid neoplasms in 224 cases. Results showed that MPL mutations occur in myeloid neoplasms including primary myelofibrosis, essential thrombocytosis, myeloproliferative neoplasm, unclassifiable, polycythemia vera, refractory anemia with ring sideroblasts and marked thrombocytosis, and myeloid neoplasms associated with PDGFB rearrangement. Compared to cases with no MPL mutations (MPL-), MPL+ cases are associated with lower hemoglobin, lower WBC counts, older age, higher reticulin scores, and lower bone marrow cellularity. Compared to MPL-/JAK2+ (with JAK2 mutations), MPL+/JAK2- (with no JAK2 mutation) cases are associated with lower hemoglobin, lower WBC counts, lower bone marrow cellularity, but no significant differences in reticulin scores or patient age. Compared to MPL-/JAK2-, MPL+/JAK2- cases show significantly higher reticulin scores, but no statistical differences in hemoglobin, WBC counts, patient age, or bone marrow cellularity. MPL and JAK2 V617F mutations can coexist (7.9%); however, MPL mutations and BCR/ABL appear mutually exclusive. Overall incidence of cytogenetic abnormalities was not significantly different in cases with or without MPL mutations. In this study, MPL positivity alone does not appear to result in a distinct entity.