Background: Essential thrombocythemia (ET) and polycythemia vera (PV) are chronic myeloproliferative neoplasms (MPN) associated with a risk of transformation to myelofibrosis (MF) and acute myeloid leukemia (AML). The clinical relevance of prior malignancy (PM) in patients (pts) with ET and PV is largely unknown. We report the prevalence of PM in ET or PV pts and its clinical implications. Methods: We performed retrospective chart review of all pts with ET and PV seen at MD Anderson Cancer Center (diagnosis according to WHO criteria) between January, 1960 and September 2010, for evidence of PM. We recorded the prior pathological diagnosis of PM, and performed a univariate analysis of age at diagnosis of MPN, sex, JAK2 status, CBC, and cytogenetics in pts with or without PM. Results: A total of 437 pts charts (ET 263, PV 174) were evaluated. 40% of pts were male (ET 33% and PV 49%). 45 pts had PM [26 ET (10%), 19 PV (11%)] with median time to diagnosis of 65 months (4-435) in ET pts and 75 months (4-570) in PV pts. 2 pts had 2 PM. Majority had solid tumors [14 Skin (ET 8, PV 6), 7 prostate (ET 4, PV3), 5 gynecologic (ET 4, PV 1), 4 breast (ET 3, PV1), 4 melanomas (ET 3, PV 1), 3 colon (ET 1, PV 2), 3 thyroid (ET 2, PV 1), 3 sarcomas (ET 2, PV 1), 4 other cancers]. Median age at diagnosis of MPN was higher in pts with PM (years; all pts: 60 vs. 48 (p<0.001); ET 57 vs. 47 (p=0.001); PV 67 vs. 50 (p<0.001), respectively). No significant difference in abnormal cytogenetics frequency between 2 groups was observed (13% for PM vs 7%; p = 0.21). The risk of progression to AML (2% vs 0.8%) or MF (9% vs 3 %) was higher in pts with PM (p=0.027). Median overall survival from MPN diagnosis was lower in PM pts(months; all pts: 182 vs. 324 (p<0.001); ET: 268 vs. 474 (p =0.01); PV: 182 vs. 322 (p=0.003), respectively), perhaps due to their age difference. No differences were found in the frequency of JAKV617F2 mutation and blood counts at diagnosis between 2 groups. Conclusions: In our experience, ET and PV pts with PM are older at MPN diagnosis and harbor increased risk of progression to MF or AML. Larger studies are needed to confirm our findings