OBJECTIVES: Transferrin saturation (TSAT) 20% or less is considered to represent functional iron deficiency in the context of malignant disease, phenomenon mediated through inflammatory changes of iron homeostasis. We aimed to investigate clinical and prognostic significance of low TSAT in patients with primary (PMF) and secondary myelofibrosis (SMF), malignant diseases characterized by strong inflammatory milieu. ----- METHODS: We retrospectively analyzed 87 patients with myelofibrosis and compared TSAT with disease specific parameters. ----- RESULTS: One-third of patients had TSAT ≤20%. Lower TSAT was significantly associated with Janus-kinase-2 (JAK2) mutation (P = 0.007), transfusion independency (P = 0.003), higher platelets (P = 0.004), lower mean-corpuscular-volume (P < 0.001), lower ferritin (P < 0.001), higher absolute-neutrophil-count (P = 0.027), lower absolute-lymphocyte-count (P = 0.041) and lower albumin (P = 0.018). PMF patients presenting with low TSAT (≤20%) experienced significantly shorter overall-survival (OS) (HR = 2.43; P = 0.017), whereas TSAT did not affect OS of SMF patients (HR = 1.48; P = 0.623). Low TSAT remained significantly associated with inferior OS in PMF in a series of multivariate Cox regression models comparing its properties to anemia, transfusion dependency, ferritin and Dynamic-International-Prognostic-System (DIPSS). ----- CONCLUSIONS: Low TSAT has detrimental effect on survival of PMF patients. This effect is independent of anemia and of ferritin levels that seem to be better at representing iron overload in PMF patients.