Here, we report a case of ESC-RCC characterized by eosinophilic cytoplasm with characteristic immunohistochemical markers (CK20-positive/CK7-negative) and a nonsense mutation in TSC2. Our analysis and summary of the clinical data, morphological characteristics, immunohistochemistry, and molecular findings of the disease will deepen our understanding of this novel renal neoplasm and help practitioners make pathological and differential diagnoses. This evidence concerns the gene TSC2 and renal cell carcinoma.