While we recognize that it is unclear whether all the same gene fusions described in TFE3-rearranged renal cell carcinoma and TFE3-rearranged PEComa are truly identical, one possible explanation for why the same gene fusions can drive tumorigenesis and result in neoplasms with differing morphology and immunophenotype is that the effects of the same translocation may vary depending on the cell type. The gene discussed is TFE3; the disease is renal cell carcinoma.