This paper discusses recently published data on mitochondrial DNA (mtDNA) extracted from Stone Age burials in Lithuania in a broader European context, and data from modern Lithuanians on the basis of recent literature. Several major processes (initial Palaeolithic colonisation, recolonisation after the LGM and Younger Dryas cold relapse, the spread of the Neolithic, and possible small-scale migrations in the Eneolithic age) could have left traces on the modern gene pool. From four Lithuanian samples where data on mtDNA were available, one (Spiginas 4) belonged to haplogroup U4, and three (Donkalnis 1, and Kretuonas 1 and 3) to U5b2. In total, out of 17 individuals from Central and East European non-farming cultures (Mesolithic and Neolithic Ceramic, spanning a period from circa 7800 BC to 2300 BC), a majority of them had mtDNA type ‘U’. An exceptionally high incidence of U5-types (more than 45%) occurs among the modern Saami (Lapps) of northern Scandinavia, perhaps the closest modern European equivalent of Mesolithic hunter-gatherers. Genetic time estimates based on modern mtDNA have suggested that the U5-type arose by mutation about 50,000 to 40,000 years BP. This age implies that around the glacial maximum 20,000 years BP, U5 types were already present and could have repopulated Central and northern Europe as soon as northern areas were deglaciated. Both western (Franco-Cantabrian) and eastern (Pontic) refugia could be sources of this repopulation. In the recent Lithuanian population, U5 and U4 haplogroups are infrequent. The mtDNA homogeneity observed across modern Europe is a more recent phenomenon, less than 7,000 years old, according to these ancient mtDNA results. We can refer to the third millennium BC, internal European migrations from the Eneolithic that significantly modified the genetic landscape, as a time window little explored by archaeogeneticists. The imprecise chronology of mtDNA mutations should in the first instance be based on audited archaeological sources.