Association of myeloproliferative neoplasm (MPN) with lymphoproliferative neoplasm (LPN) has been occasionally reported. The aim of this study, which included 353 patients with polycythemia vera and 467 with essential thrombocythemia, was to assess whether the risk of developing LPN is increased in MPN patients. Expected numbers of LPN incident cases were calculated based on 5-year age group, gender, and calendar time-specific cancer incidence rates in the general population of the same area. Standardized incidence ratios were computed to estimate the relative risk of developing LPN. Analyses were carried out for the whole series and then separately for essential thrombocythemia and polycythemia vera, gender, and JAK2V617F genotype. With 4,421 person-years, we found 11 patients developing LPN, including four chronic lymphocytic leukemias, five non-Hodgkin's lymphomas, and two plasma cell disorders, after a median interval time of 68 months from MPN diagnosis. Cumulative risk to develop LPN at 5 and 10 years was 0.93% (95% confidence interval, 0.39-2.22) and 2.96% (95% confidence interval, 1.52-5.72), respectively. There was a 3.44-fold increased risk of LPN compared with the general population, ranging from 2.86 for plasma cell disorder to 12.42 for chronic lymphocytic leukemia; the risk was significantly increased in JAK2V617F mutated patients (5.46-fold) and in males (4.52-fold). The JAK2V617F mutation was found in lymphoid tumor cells in two of three cases evaluated, indicating that, in some patients, LPN originated in a JAK2V617F mutated common lymphoid-myeloid hematopoietic progenitor cell. We conclude that the risk of developing LPN is significantly increased in MPN patients compared with the general population.