Myeloproliferative neoplasms (MPNs) have estimated annual incidence rates for polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis of 0.84, 1.03, and 0.47 per 100,000. Prevalence is much higher, particularly for PV and ET, as mortality rates are relatively low. Patients are often concerned about why they developed an MPN and epidemiological studies enable the identification of potential causative factors. Previous work in small heterogeneous studies has identified a variety of risk factors associated with MPNs including family history of MPN, autoimmune conditions, some occupational exposures, and blood donation. At a population level, germline predisposition factors in various populations have been associated with MPNs. The pilot MOSAICC (Myeloproliferative Neoplasm: An In-depth Case-Control) study is one of the largest epidemiological studies in MPN ever carried out to date. It demonstrated the most effective methods for carrying out a significant epidemiological study in this patient group including the best way of recruiting controls, as well as how to evaluate occupational and lifestyle exposures, evaluate symptoms, and collect biological samples. Significant results linked to MPNs in the pilot study of 106 patients included smoking, obesity, and childhood socioeconomic status. The methodology is now in place for a much larger ongoing MOSAICC study which should provide further insight into the potential causes of MPNs.