Besides renal cell carcinoma with TFEB translocation, TFEB-amplified renal cell carcinoma is a distinct group of tumors with amplification of the 6p21 locus harboring TFEB. The TFEB amplification (commonly observed by fluorescence in situ hybridization) leads, as downstream effects, to TFEB overexpression (Figure 2) [35,36,37,38,39]. This evidence concerns the gene TFEB and hereditary clear cell renal cell carcinoma.