Eosinophilic solid and cystic renal cell carcinomas (ESC RCC) is a rare, unique tumor type not yet included in the World Health Organization classification of renal neoplasia. Separately, RCCs found in patients with tuberous sclerosis complex (TSC) have recently been categorized into 3 morphologic groups: RCC with a tubulopapillary architecture separated by smooth muscle stroma, chromophobe-like, and eosinophilic-microcytic type. The third classification has been identified in ∼11% of TSC-associated RCC and have histology identical to ESC RCCs. The sporadic form of ESC RCC, not associated with TSC, have only been characterized on the cytogenetic level and the full molecular underpinnings have yet to be examined. Using next-generation sequencing we present 2 cases of sporadic ESC RCC in patients without clinical features of tuberous sclerosis, which demonstrate pathogenic somatic TSC2 gene mutations. These mutations are without other alterations in any other genes associated with RCC, suggesting that sporadic ESC RCC may be characterized by somatic tuberous sclerosis gene mutations (TSC2).