The fully vegetated summits of the table mountains that form the Guayana Highlands (GH), in northern South America, hold amazing biodiversity and endemism levels, and unique vegetation types. In spite of their present-day healthy appearance, their biota is seriously threatened of habitat loss by upward displacement, because of the projected warming for the end of this century. Available data are still insufficient for a definite assessment, but preliminary estimations based on representative endemic vascular plant species show that roughly one-tenth to one-third of them would loss their habitat with the 2–4°C temperature increase predicted for the region by AD 2100. Given the underlying endemism, the eventual loss of biodiversity will be of global nature. Other mountain ranges around the world with similar characteristics of the GH, namely topographical isolation, high endemism and absence of nival stage because of the lower altitude, would be under similar unexpected risk, and should be urgently considered for conservation purposes.