Two fossilized human crania (Apidima 1 and Apidima 2) from Apidima Cave, southern Greece, were discovered in the late 1970s but have remained enigmatic owing to their incomplete nature, taphonomic distortion and lack of archaeological context and chronology. Here we virtually reconstruct both crania, provide detailed comparative descriptions and analyses, and date them using U-series radiometric methods. Apidima 2 dates to more than 170 thousand years ago and has a Neanderthal-like morphological pattern. By contrast, Apidima 1 dates to more than 210 thousand years ago and presents a mixture of modern human and primitive features. These results suggest that two late Middle Pleistocene human groups were present at this site—an early Homo sapiens population, followed by a Neanderthal population. Our findings support multiple dispersals of early modern humans out of Africa, and highlight the complex demographic processes that characterized Pleistocene human evolution and modern human presence in southeast Europe.