International audienceAims: tissue defects, resulting from surgical resection of oral squamous cell carcinoma (OSCC), are routinely reconstructed with skin graft. OSCC arising from the grafted skin have been described, however, it is still unclear whether primary and second tumours have a common clonal origin. By screening mitochondrial DNA D-loop region (mtDNA), we evaluated the clonal relationship between the primary OSCC and the second neoplastic features appearing in the skin graft in three patients. Methods and Results: in all the three cases, the neoplastic lesions arising in the skin graft showed a clonal relationship with the previous OSCC and, on the basis of the results obtained with the mtDNA analysis, could be considered a recurrence of the primary OSCC rather than a second primary OSCC. Conclusions: Starting from a field of genetically altered cells of the oral mucosa, the spreading of the clonal cell population to the cutaneous flap might be stimulated by cytokines produced by the grafted skin. More studies are needed to evaluate the molecular relationship between primary and second OSCC to identify patients at higher risk of developing a second tumour of the skin graft
