TFE3, known as Transcription Factor E3, is a member of the helix- loop-helix family of transcription factors. TFE3 interacts with several transcriptional regulators to affect cell growth, proliferation and osteoclast and macrophage differentiation. In the immune system, TFE3 plays important roles in modulating immunoglobulin heavy- chain expression and regulating B cell activation. Additionally, TFE3 participates in insulin signaling and may play a role in enhancing insulin sensitivity. The TFE3 gene is located on chromosome Xp11.2. Translocations within this region generates TFE3 gene fusion products and clinically manifests as Xp11.2 translocation renal cell carcinoma (Xp11 TRCC), alveolar soft part sarcoma, perivascular epithelioid cell tumor, and epithelioid hemangioendotheliomas. Since translocation can lead to overexpression of nuclear TFE3 and is a marker of metastasis and poor survival, immunohistochemical detection of TFE3 can be valuable as a prognostic factor, an indicator of lymph node metastasis, and a screening marker for Xp11.2 translocation before genetic analysis.