Deleterious mutations in PBRM1 are frequent in cancer, especially in clear cell renal cell carcinoma where they are an early driver event occurring subsequent to VHL alteration in approximately 40% of patients – representing ≈ 175,000 new cases worldwide every year. Until recently, PBRM1 defects were often overlooked in clinical practice because there was no technology with sufficient sensitivity available to detect them. Despite recent advances made to better diagnose PBRM1 mutations, notably thanks to the advent of next-generation sequencing, patients with PBRM1-defective cancers (including but not restricted to clear cell renal cell carcinomas) still lack treatment options, which represents an important unmet medical need.