RB1 (RB transcriptional corepressor 1, a.k.a. pRb) is a well characterized tumor-suppressor gene, located on 13q14.2; bi-allelic inactivation of the RB1 gene due to mutations and/or deletions is causal for the development of retinoblastoma (RB) as well as bladder cancer. The protein encoded by this gene is a negative regulator of the cell cycle and was the first tumor suppressor gene found. The encoded protein also stabilizes constitutive heterochromatin to maintain the overall chromatin structure. The active, hypophosphorylated form of the protein binds transcription factor E2F1. Deletions of the RB1 locus are also common in a wide variety of solid tumors and hematologic malignancies including chronic lymphocytic leukemia, multiple myeloma, acute myelocytic leukemia, myelodysplastic syndrome, and chronic myeloproliferative disorders. Hence, Fluorescence in situ Hybridization is a valuable tool for the detection of RB1 gene deletions and can be used in combination with further biological markers, morphology and clinical information for the prediction of disease progression and overall survival.