To report a rare case of undifferentiated intimal sarcoma (UIS) of the pulmonary artery in a 44-year-old woman, and to study it by electron microscopy and a novel immunohistochemical (IHC) panel that recognizes markers of endothelial and haematopoietic stemness, in order to extend current knowledge about the histogenesis of this rare neoplasm. Immunohistochemical reactions for CD31, CD34, α-smooth muscle actin (α-SMA), caldesmon, calponin, actin, desmin, epithelial membrane antigen, WT1, CD117, Ki67, nestin, RUNX-1, platelet-derived growth factor, NG2, CD44, CD90 and CD105 were performed manually or automatically. Neoplastic cells were negative for CD31 and CD34, but positive for calponin, nestin, WT1, CD44, and RUNX-1. Electron microscopy was performed after osmium tetroxide fixation and staining with lead citrate and uranyl acetate. Ultrastructurally, tumour cells had slightly irregular nuclei, cisternae of rough endoplasmic reticulum, and punctate intercellular junctions. We report a case of pulmonary artery UIS expressing previously unreported markers, i.e. RUNX-1, nestin, WT1, and CD44, that are commonly seen in different stages of the vascular differentiation hierarchy. These findings, together with the negativity for mature endothelial and smooth muscle markers, raise the question of whether this neoplasm may derive from a vessel wall-resident stem cell, such as the haemangioblast or an embryonic-like stem cell. © 2012 Blackwell Publishing Ltd.