Vitamin D insufficiency is commonly observed in the general population; observational studies have suggested an association with increased risk of cancer development. We examined the clinical and prognostic relevance of low plasma levels of 25-hydroxyvitamin D (25[OH]D) in myeloproliferative neoplasms (MPN) and myelodysplastic syndromes (MDS). A total of 409 patients were studied: 247 (60%) with primary myelofibrosis (PMF), 74 (18%) with de novo MDS, 63 (15%) with polycythemia vera (PV), and 25 (6%) with essential thrombocythemia (ET). Plasma 25(OH)D levels were measured by liquid chromatography-tandem mass spectrometry; a level lower than 25 ng/mL indicated vitamin D insufficiency and a level lower than 10 ng/mL indicated severe deficiency. The proportion of patients with 25(OH)D insufficiency was significantly greater in PMF (48%) and PV (43%) when compared with ET (28%) and MDS (28%) (P = 0.01). Severe 25(OH)D deficiency was significantly more frequent in ET (12%) and PMF (9%), compared with PV (3%) and MDS (1%) (P = 0.05). There were no significant correlations between 25(OH)D insufficiency, or severe deficiency, and a variety of clinical or laboratory variables in PMF, MDS, or PV. Furthermore, Vitamin D insufficiency did not influence either overall or leukemia-free survival in PMF, MDS, or PV (P > 0.05). We conclude that while hypovitaminosis D is relatively common in MPN and MDS, its clinical relevance for prognosis is limited. © 2011 Wiley-Liss, Inc.