Even though oncogenic drivers are known in these syndromes, i.e., the Folliculin (FLCN) gene for BHD and Phosphatase and Tensin Homolog (PTEN) for CS, the search for a role of such nuclear genes in triggering oncocytic transformation has failed to date, and it is likely therefore that other modifiers impinge on the phenotypic change that occurs in a few, but not all syndromic individuals. The gene discussed is PTEN; the disease is Cowden syndrome 1.