Tooth crown tissue proportions and enamel thickness distribution are considered reliable characters for inferring taxonomic identity, phylogenetic relationships, dietary and behavioural adaptations in fossil and extant hominids. While most Pleistocene hominins display variations from thick to hyper-thick enamel, Neanderthals exhibit relatively thinner [1-3]. Moreover, studies of the external and internal dental structures documented the existence of a temporal trend in the structural organization of the European Neanderthal lineage [1-4]. However, the chronological and geographical origin for the appearance of this typical Neanderthal condition is still unknown. Comparative studies on the Early Pleistocene species of Homo antecessor (Gran Dolina-TD6 site, Sierra de Atapuerca) identified anatomical traits shared with the Neanderthal clade . In this context, the European population from TD6 represents an excellent opportunity to investigate the appearance of the derived (thin) enamel condition. In this study, we aim to test the hypothesis if H. antecessor molars approximates the Neanderthal condition for tissue proportions and enamel thickness. To do so, for the first time we characterised the molar inner structural organization in this Early Pleistocene hominin population (n=17) and compared it to extinct and extant populations of African, Asian and European origin. We used high-resolution images to investigate the structural configuration of TD6 molars (tissue proportions, enamel thickness and distribution). TD6 molars in cluded in the study exhibit wear degree between 1 (no occlusal wear) and 3 (small dentine patches). Following established protocols [1-3] we measured and calculated three sets of variables. For the 2D estimates, the complete sample was included although we performed cusp reconstruction. For the 3D estimates, complete crown, 13 molars were included (excluding the four molars exhibiting wear degree 3). In order to extract the largest amount of information of the TD6 specimens, including the occlusal worn molars, we assessed lateral (non-occlusal) enamel thickness. Adjusted Z-score of the three variables accounting for tissue proportions (percentage of dentine, average and relative enamel thickness) were computed to compare 2D and 3D dental tissue proportions and enamel thickness values of the TD6 specimens to the means and standard deviations of the Neanderthal and modern human groups. This statistical method allows the comparison of unbalanced samples by using Student’s inverse t distribution [1,3]. To visualize enamel thickness topographic distribution in TD6, 3D chromatic maps were generated. For comparative purposes, we generated the chromatic maps of a selected sample of specimens of European and African origin. The results showed that TD6 permanent molars exhibit thick average and relative enamel in 2D and 3D estimates. This condition, regarded as primitive trait, is shared with the majority of extinct and extant hominin sample, except for Neanderthals and some isolated specimens, such as African Early Pleistocene specimen from Eritrea. However, while the total crown percent of dentine in TD6 globally resembles the low modern values, the lateral crown percentage of dentine tend to be much higher, closer to the Neanderthal signal. Similarly, the H. antecessor molar enamel distribution maps reveal a relative distribution pattern that is more similar to the Neanderthal condition (with the thickest enamel more spread at the periphery of the occlusal basin) rather than that of fossil specimens and modern humans (with thicker cuspal enamel). Future studies on European Middle Pleistocene populations will provide more insights into the evolutionary trajectory of the typical Neanderthal dental structural organization.