Patients living with myeloproliferative neoplasms (MPN) have up to 20% risk of developing bone marrow fibrosis. The only way to detect fibrosis is through bone marrow examination performed when there are changes in blood counts, appearance on the blood film or development of new symptoms. Megakaryocytes have characteristic abnormalities in MPN, and these progress with fibrosis. We therefore hypothesise that the gene expression profile of platelets undergo specific changes with progression to marrow fibrosis. A transcriptome next-generation sequencing approach was used to analyse the expression of >20,800 genes in platelets from 74 individuals. A training cohort of 25 MPN patients and 15 controls were analysed and a fibrosis-associated platelet transcript signature was generated. The signature was then validated using a test cohort of 34 MPN patients. We identified a large number of differentially expressed genes in platelets from patients compared to controls and more than 1,000 of these were uniquely differentiated in platelets from patients with marrow fibrosis. Of these, 96 genes were orthogonally verified and a putative 3-gene fibrosis-associated signature was identified and assessed on the test cohort. This putative signature could discriminate between patients with and without fibrosis with 88% accuracy (93% negative-predictive value, 71% positive predictive value and area under the ROC curve = 0.82). Together, our work shows that there are specific changes in platelet gene expression in MPN and that this approach has potential to be used as a blood-based surrogate marker for pathological fibrosis in MPN.