Several studies have reported frequent loss of PTEN expression, detected via IHC or FISH analysis, in up to 51% of SDC.15, 37 In head and neck squamous cell carcinoma, tumor cells with PTEN loss were shown to be commonly resistant to pan‐PI3K inhibitors; however, in vitro studies have shown promising results for targeted PI3K therapy in SDC cells.15 Finally, the discovery of a TBL1XR1‐PIK3CA fusion, which has been reported to result in overexpression of the complete PIK3CA protein, in one of our cases further supports the important role of PIK3CA in the oncogenesis of SDC.39 This evidence concerns the gene PTEN and head and neck squamous cell carcinoma.