Chromosomal abnormalities are frequent in chronic lymphocytic leukemia (CLL), and most have prognostic value. In addition to the four well-known abnormalities (13q, 11q and 17p deletions, and trisomy 12), other recurrent aberrations have been linked to the disease outcome and/or drug resistance. Moreover, the complex karyotype has recently emerged as a prognostic marker for patients undergoing immunochemotherapy or targeted therapies. Here, we describe the main chromosomal abnormalities identified in CLL and related disorders (small lymphocytic lymphoma and monoclonal B-cell lymphocytosis) by reviewing the most recent literature and discussing their detection and clinical impact. Lastly, we provide technical guidelines and a strategy for the cytogenetic assessment of CLL.