Aggressive variant prostate cancer (AVPC), a subset of prostate cancers that share the clinical, therapy response, and molecular profiles of the small cell prostate carcinomas, has been characterized by a molecular signature of combined tumor suppressor defects in TP53, RB1, and/or PTEN (AVPC-TSGs), determined by either immunohistochemistry (IHC) or genomic analysis [9]. The gene discussed is RB1; the disease is prostate cancer.