X-linked thrombocytopenia with thalassemia (XLTT) is caused by the mutation 216R>Q in exon 4 of the GATA1 gene. Male hemizygous patients display macrothrombocytopenia, splenomegaly and a β-thalassemia trait. We describe two XLTT families where three males were initially misdiagnosed as having primary myelofibrosis (PMF) and all 5 investigated males showed mild-moderate bone marrow (BM) reticulin fibrosis. Comparative investigations were performed on blood samples and BM biopsies from males with XLTT, PMF patients and healthy controls. Like PMF, XLTT presented with high BM microvessel density, low GATA1 protein levels in megakaryocytes, and elevated blood CD34+ cell counts. But unlike PMF, the BM microvessel pericyte coverage was low in XLTT, and no collagen fibrosis was found. Further, as evaluated by immunohistochemistry, expressions of the growth factors VEGF, AGGF1 and CTGF were low in XLTT megakaryocytes and microvessels but high in PMF. Thus, although the reticulin fibrosis in XLTT might simulate PMF, opposing stromal and megakaryocyte features may facilitate differential diagnosis. Additional comparisons between these disorders may increase the understanding of mechanisms behind bone marrow fibrosis in relation to pathological megakaryopoiesis. This article is protected by copyright. All rights reserved.