A complete pre-agricultural European human genome from a ∼7,000-year-old Mesolithic skeleton suggests the existence of a common genomic signature across western and central Eurasia from the Upper Paleolithic to the Mesolithic, and ancestral alleles in several skin pigmentation genes suggest that the light skin of modern Europeans was not yet ubiquitous in Mesolithic times. The emergence of agriculture is thought to have caused many of the evolutionary changes in human physiology evident in the fossil record. Precisely which changes it is hard to say in the absence of a baseline — a record of human physiology just before the advent of farming. We may now have that in the form of a genome of a Mesolithic hunter-gatherer from Spain, described by Carles Lalueza-Fox and colleagues this week. The genes of this male, who lived around 7,000 years ago, had more in common with ancient genomes from Siberia than with other Europeans, suggesting a wide if thinly spread genetic continuity across Eurasia. He would have been lactose intolerant and less able to digest starchy foods than Neolithic farming people, suggesting that these changes came in with agriculture. He would also have had the unusual combination of dark skin and blue eyes, suggesting that in Mesolithic times, the transition to a lighter, more modern European skin tone was incomplete and that changes in eye colour came first. Ancient genomic sequences have started to reveal the origin and the demographic impact of farmers from the Neolithic period spreading into Europe1,2,3. The adoption of farming, stock breeding and sedentary societies during the Neolithic may have resulted in adaptive changes in genes associated with immunity and diet4. However, the limited data available from earlier hunter-gatherers preclude an understanding of the selective processes associated with this crucial transition to agriculture in recent human evolution. Here we sequence an approximately 7,000-year-old Mesolithic skeleton discovered at the La Braña-Arintero site in León, Spain, to retrieve a complete pre-agricultural European human genome. Analysis of this genome in the context of other ancient samples suggests the existence of a common ancient genomic signature across western and central Eurasia from the Upper Paleolithic to the Mesolithic. The La Braña individual carries ancestral alleles in several skin pigmentation genes, suggesting that the light skin of modern Europeans was not yet ubiquitous in Mesolithic times. Moreover, we provide evidence that a significant number of derived, putatively adaptive variants associated with pathogen resistance in modern Europeans were already present in this hunter-gatherer.