The expansion of the Danubian Neolithic, the dense settlement in the loess plains, the preservation of thousands of graves and the recent development of preventive archaeology have greatly increased our knowledge of the first Neolithic peoples??? way of life in Alsace. If we consider the Mesolithic people of North Africa (Taforalt, Maroc) and Ukraine (Vasiliyevka II and III. ; Vovnigi II) as precursors of cranial surgery, the first Danubian (Vedrovice, Moravie) and Mediterranean Neolithic people (abri Pendimoun, Castellar, Var) show early use of trepanation to treat trauma or other pathologies. Four cases of this surgical procedure found in archaeological contexts in Alsace have been published.One of the oldest identified cases comes from a recent Rubane cemetery at Hoenheim-Souffelweyersheim (Bas-Rhin). One of the graves housed an old man with a large right frontal depression with a perforation in the centre. Bone splinters seem to have been extracted after the trauma occurred.The operative choice was that of an abrasion of the external table and the diploe. However, it is difficult to comment on the origin of the perforation, choice or consequence of the bone thinning. Another skull from the same site bears the marks of an impact framed by two incisions.For these two cases, an observation phase preceded the choice of the medical protocol.Other cranial lesions observed on Early and Middle Neolithic subjects from Alsace show the difficulty of the diagnosis with the pathological aspects having to be disentangled from the surgical aspects.In the Danubian cemetery of Ensisheim "Les Octrois" in the Haut-Rhin, tomb 44 yielded the remains of a subject whose cranial vault shows two large depressions TR-1 (6.5 mm x 63 m) and TR-2 (95 mm x 91 mm), located on the central axis and interpreted upon discovery as scarred craniectomies. The diagnosis for TR-1 was mainly based on the newly formed bony laminae that would have covered the entire bony surface of the opening. Observation of this arch defect identifies a raised centre around which radiate five depressions. The diagnosis proposed by K. W. Alt and collaborators (1997) involved the perforation being made by successive circular scrapings and the said perforation would have been filled with scarred bone. Similar frontal alterations, published in the anthropological literature, have been the subject of different diagnoses. Significant healed frontal trepanations are known for the periods ranging from the Late Neolithic to the Bronze Age (at the Trou de Goujout in Teyjat, in the Dordogne, for example). Healed, they show no filling ofthe gap. The differential diagnosis for this TR-1 defect could point to osteolytic erosion of the cranial vault followed by scarring. The TR-2 alteration was interpreted by the authors as a partially healed trepanation with a procedure consisting of an act of scraping after the development of four linear incisions defining a surface of the external table.Other pathologies, initiating osteolysis of the cranial vault, cannot be excluded, including that of a traumatic episode leading to hematoma and that of osteitis, which subsequently healed, due or not to human intervention. Whatever the possible diagnosis, that of the bone growth was effective enough to fill such a large area has, to our knowledge, never been mentioned in neurosurgery or paleoanthropology papers (Nerlich et al., 2003 ; Partiot et al., 2020). It is therefore necessary, in the future, to look at the healing and regrowth processes of cranial bone in the light of a well-supported differential diagnosis.The necropolis of Lingolsheim (Bas-Rhin) dating to the Middle Neolithic Grossgartach yielded the burial of a young adult with rich grace goods. The individual had a cranial lacuna described as a double trepanation (Forrer, 1938). The loss of bone affects the bregma, the left parietal and slightly the right parietal. The phases of alteration and healing of the edges of the orifice make it possible to identify a series of events that led to the perforation of the cranial bone and its pathological, taphonomic or anthropogenic origin provides subject for discussion. Chronologically, three episodes probably shaped this cranial opening. Firstly, a localized osteolytic lesion of exocranial development, well circumscribed, led to a bregmatic perforation of the two tables and of the diploe. The only observation of the edge, abrupt, without bevel, with a slightly sinuous, jagged outline and an apparent diploe and a blunt ridge, could suggest the pathological and osteolytic origin of this perforation. The use of an interactive tool has made it possible to support this differential diagnosis (Partiot et al., 2017). Menigocele, gliocele cyst and isolated eosinophilic granuloma (Langerhansian histiocytosis) are pathologies that may have generated this orifice; but due to the lack of a possible histological analysis, this remains hypothetical. A surgical opening made in two phases by grooving-chiseling widened the gap, which was of pathological origin. The first opening, according to the healing of its bevel was cut on the left parietal. The only trace of this surgical act, a 12 mm length fragment of a slightly inclined external bevel, is completely healed. A second intervention enlarged the scarred opening. The hypothesis of post-mortem cutting or trepanation followed by immediate death can be rejected as the blunt edges of the two bone tables attest to an engaged healing process. We cannot exclude the possible link between these two interventions and the pathological orifice. Coalescence and the development of tumours from an eosinophilic granuloma may have warranted the second intervention, following external manifestations of soft tissue swelling. The surgical opening therefore includes two operations and not just one as was initially mentioned. The first individual survived the intervention by several years whereas the second only for a few months.The trepanned individual from Riedisheim (Haut-Rhin) is the most recent from Alsace. The archaeological context remains vague, Final Neolithic or Early Bronze Age, for this burial discovered during quarry work around 1888. A roughly triangular parietal gap occupies the centre of a large abraded cranial surface that evokes an act of the thinning of the vault followed by an action of cutting a shutter or enlarging the orifice. The cut marks that are still visible despite notable scarring of the edges indicate trepanation.With this overview, we note that these surgical acts remain rare in Alsace in relation to the total number of burials dating from the Early Neolithic to the Bronze Age. There is no local extension of the practice. Most of the individuals survived the interventions that would have been the treatment for trauma or pathology. The case from Ensisheim may have been a surgical act, but in this specific case, the marks do not seem to be due to healed trepanations and an additional study is needed.