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Philadelphia-negative myeloproliferative neoplasms (MPNs), essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF), are rare clonal hematopoietic stem cell disorders accompanied by a strong inflammatory milieu, which is directly responsible for constitutional symptoms associated with the disease, such as fever, weight loss or night sweats. Non-hematologists sometimes (and often wrongly) consider the fever in MPN patients to be a symptom of an underlying disease, which may have devastating consequences. Serum procalcitonin (PCT) is a circulating biomarker commonly used to improve the diagnostic accuracy of bacterial infections and to guide antibiotic therapy. The aim of this study was to test whether PCT could aid the clinician in the early diagnosis of bacterial infections in MPNs. This study investigated PCT in 41 ambulatory MPN patients (13 ET, 13 PV and 15 MF) who had no signs of infection and compared it to 10 MPN patients with microbiologically and/or serologically documented bacterial infections. Median PCT in MPN patients was 0.02 ng/mL (range 0.01–0.09 ng/mL). No difference in PCT was found between ET, PV and MF patients (p = 0.993), whereas MPN patients with documented bacterial infections had significantly higher PCT (median PCT 2.45, range 0.90–5.40 ng/mL) when compared to MPN patients with (median PCT 0.03 ng/mL) or without constitutional symptoms (median PCT 0.02 ng/mL; p < 0.001 for both analyses). These results clearly show that PCT should not be considered as a disease biomarker in MPNs and careful clinical assessment for the signs of infection is needed when MPN patients present with fever and high PCT.