Non-Hodgkin lymphomas represent a frequent complication of human immunodeficiency virus (HIV) infection, occurring at higher frequency than in immunocompetent individuals, and causing morbidity and mortality. Here, we present the method we have followed to analyze the genomic lesions in HIV-related and in other immunodeficiency-related lymphomas, as well in diffuse large B-cell lymphoma (DLBCL) samples derived from immunocompetent hosts. The technology we have used is represented by the GeneChip Human Mapping 250K NspI arrays (Affymetrix, Santa Clara, CA, USA), arrays based on 25mer oligonucleotides initially designed for large-scale genotyping, that is, the detection of thousands of single-nucleotide polymorphisms (SNPs), then shown to be applicable for the detection of cancer alterations. The protocol is shown in all its steps with suggestions and tips. Applications of the technology and obtained results are also briefly summarized.