All the RCC subtypes with clear cell phenotype (i.e. TFE3 or TFEB translocation RCCs, TCEB1-mutated RCC [18], RCC with 8p monosomy [19], RCC with prominent smooth muscle stroma (RCCSMS) [20–25] and RCC associated with von Hippel-Lindau syndrome) can exhibit a CCPRCC-like histomorphology [26, 27], but CCRCC cases pose the biggest difficulty because this tumor type is the most common and it also has some morphological similarities. The gene discussed is TFEB; the disease is renal cell carcinoma.