Although benign, pituitary adenomas frequently invade adjacent sinuses or recur after first surgery. To date, there is no histological marker predictive of recurrence. Angiogenic factors are candidate markers. Endocan is a proteoglycan secreted by endothelial cells, associated with an aggressive behavior in several tumor types. Endocan expression was investigated by immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR) in 18 normal post-mortem pituitaries and in 107 patients operated for a pituitary adenoma (with a follow-up of at least 8 years after surgery). In normal pituitaries, endocan was never observed in vessels but was detected in isolated endocrine cells. In adenoma tissue, we found a strong association between endocan immunoreactivity in endothelial cells and progression (P = 0.0009), as well as tumor size (P = 0.0012), raised mitotic count (P = 0.02) and p53 expression (P = 0.032). Morphometric analysis of the microvessels showed that the mean vessel area was significantly higher in the subgroup of tumors with an endothelial expression of endocan (P = 0.028), coherent with the neoangiogenesis process occurring in the pituitary. The immunolabeling of endocan in endothelial cells may therefore appear to be a relevant marker of aggressive behavior in pituitary tumors.