In order to systematically analyze the potential applicability of treatments based on SWI/SNF-deficiency—including dependency on EZH2—to bladder cancer, we comprehensively dissected the frequency of inactivating alterations in known SWI/SNF subunit genes in bladder carcinomas revealing ARID1A truncating mutations as the most common inactivating events in SWI/SNF complexes. Here, EZH2 is linked to urinary bladder cancer.