Significance Renal cell carcinomas (RCCs) are heterogeneous malignancies thought to arise from kidney tubular epithelial cells, and clear cell RCC is the most common entity. This study demonstrates that cell atlases generated from benign kidney and two common RCCs using single-cell RNA sequencing can predict putative cells of origin for more than 10 RCC subtypes. A focused analysis of distinct cell-type compartments reveals the potential role of tumor epithelia in promoting immune infiltration and other molecular attributes of the tumor microenvironment. Finally, an observed association between the lack of immunotherapy response and endothelial cell fraction has important clinical implications. The current study, therefore, significantly contributes toward understanding disease ontogenies and the molecular dynamics of tumor epithelia and the microenvironment.