Autosomal-dominant polycystic kidney disease (ADPKD) is the most common inherited renal cystic disease affecting up to 10% of patients requiring some form of renal replacement therapy such as hemodialysis or kidney transplant. An association between autosomal-dominant polycystic kidney disease (ADPKD) and renal cell carcinoma (RCC) has been suspected since the 1930s. Many cases of RCC in ADPKD patients have been observed and published in the meantime. The gene mutations responsible for ADPKD have been discovered in the 1990s, however a direct genetic link to RCC has not been discovered so far, and the debate about an association between these two diseases is still controversial and ongoing. Many clinical experts who have published about this issue suspect a genetic link and state that ADPKD patients are much more prone to develop RCC than patients with end-stage renal disease (ESRD) of other causes. Currently there are no clear clinical guidelines regarding early nephrectomy in ADPKD patients with growing soft tissue nodules within their native kidneys. This commentary/ review on this important clinical issue describes the experience with these patients in one institution and gives an overview of the literature.