(6,7) The most commonly altered genes in primary prostate cancer are ETS fusions, PTEN, SPOP, TP53, and FOXA1.(8) Furthermore, in the metastatic castration resistant disease setting, alterations in AR, TP53, MYC, ZMYM3, APC, and RB1 are reported to be significantly enriched compared to primary prostate cancer.(9) Although the predictive role of many of these genomic alterations is still being explored, there is heterogeneity in interpretating the clinical significance of AR gene alterations in patients with advanced disease. The gene discussed is RB1; the disease is prostate cancer.