Simple SummaryRenal cancer is a common malignant neoplasm. Indeed, not every cancer is created equal, as there are different entities with specific morphological and molecular features. These differences also lead to different clinical behaviors, ranging from benign to highly aggressive neoplasms. In renal cancer, it is not unusual to have cystic hollow spaces. Clear cell renal cell carcinoma is the most frequent type of renal cancer, and it can be cystic. Distinguishing it from other subtypes of renal carcinomas can, in some cases, be challenging.AbstractA wide variety of renal neoplasms can have cystic areas. These can occur for different reasons: some tumors have an intrinsic cystic architecture, while others exhibit pseudocystic degeneration of necrotic foci or they have cystically dilated renal tubules constrained by stromal neoplastic cells. Clear cell renal cell carcinoma (CCRCC), either solid or cystic, is the most frequent type of renal cancer. While pseudocysts are found in high-grade aggressive CCRCC, cystic growth is associated with low-grade indolent cases. The latter also form through a cyst-dependent molecular pathway, and they are more frequent in patients suffering from VHL disease. The differential diagnosis of multilocular cystic renal neoplasm of low malignant potential and clear cell papillary renal cell tumor can be especially hard and requires a focused macroscopical and microscopical pathological analysis. As every class of renal tumor includes cystic forms, knowledge of the criteria required for a differential diagnosis is mandatory.