Significance: Neanderthals once inhabited Europe and western Asia, spreading as far east as the Altai Mountains in southern Siberia, but the geographical origin and time of arrival of the Altai populations remain unresolved. Excavations at Chagyrskaya Cave in the Altai foothills have yielded 90,000 stone artifacts, numerous bone tools, 74 Neanderthal fossils, and animal and plant remains recovered from 59,000- to 49,000-year-old deposits. The Chagyrskaya Neanderthals made distinctive stone tools that closely resemble Micoquian artifacts from eastern Europe, whereas other Altai sites occupied by earlier Neanderthal populations lack such artifacts. This suggests at least two dispersals of Neanderthals into southern Siberia, with the likely ancestral homeland of the Chagyrskaya toolmakers located 3,000 to 4,000 kilometers to the west, in eastern Europe.