BACKGROUNDPatients with myeloproliferative neoplasms (MPNs) experience a high persistence, prevalence, and severity of fatigue. There is currently only limited information regarding factors that contribute to fatigue in patients with MPNs. METHODSA 70-item, Internet-based survey regarding fatigue was developed by MPN investigators and patients/advocates and hosted by the Mayo Clinic Survey Research Center. RESULTSFatigue was found to be prevalent and severe among international survey respondents (1788 respondents). Higher body mass index (P<.001), current use of alcohol (P<.001), and current tobacco use (P=.0025) were found to be significantly associated with greater fatigue. Moderate/severe fatigue was present more frequently in those individuals who did not exercise compared with those who reported exercising at least once per week (P<.001). Medical comorbidities found to be significantly associated with greater fatigue included restless leg syndrome (P=.006), diabetes mellitus (P=.045), fibromyalgia (P<0.001), chronic fatigue syndrome (P=.006), and chronic kidney disease (P=.02). Current use of antidepressants (P<.001), antihistamines (P=.0276), antianxiety medications (P=.0357), and prescription pain medications (P2 on the Patient Health Questionnaire, indicating a high probability of depression. Higher Brief Fatigue Inventory score, Myeloproliferative Neoplasm Total Symptom Score, and individual symptom items were all associated with a higher likelihood of depressive symptoms (P<.0001). CONCLUSIONSThe management of fatigue should be multifactorial, with a comprehensive assessment and treatment plan to address all modifiable fatigue etiologies. Patients with MPNs likely have a higher prevalence of mood disturbances compared with the general population, suggesting the need to assess and intervene in this domain. Cancer 2016;122:477-485. (c) 2015 American Cancer Society.