The BCL2L1 (BCL2-like 1, a.k.a. BCLX) gene is located in the chromosomal region 20q11.21 and encodes for an anti-apoptotic protein that belongs to the BCL2 family. These genes are involved in a wide variety of cellular activities including lymphocyte development and hematopoiesis. BCL2L1 amplifications have been reported in several human cancers including lung, ovarian breast, melanoma, and hematologic malignancies. Overexpression of BCL2L1 reduces MYC-induced apoptosis in immortalized bronchial epithelial cells. Furthermore, BCL2L1 amplifications are found in many tumor cell lines with resistance to chemotherapeutic agents. Targeting the BCL2 family proteins with small non-peptidic compounds, so called BH3-mimetics, is currently investigated in clinical trials. Hence, the identification of BCL2L1 amplifications by Fluorescence in situ Hybridization and the inhibition of BCL2L1 signaling may be of therapeutic significance in various types of tumors.