Diffuse large B-cell lymphoma is one of the most frequent mature B-cell hematological neoplasms and non-Hodgkin lymphomas. Despite advances in diagnosis and treatment, clinical evolution is unfavorable in a subset of patients. Using molecular techniques, several pathogenic models have been proposed, including cell-of-origin molecular classification; Hans’ classification and derivates; and the Schmitz, Chapuy, Lacy, Reddy, and Sha models. This study introduced different machine learning techniques and their classification. Later, several machine learning techniques and artificial neural networks were used to predict the DLBCL subtypes with high accuracy (100–95%), including Germinal center B-cell like (GCB), Activated B-cell like (ABC), Molecular high-grade (MHG), and Unclassified (UNC), in the context of the data released by the REMoDL-B trial. In order of accuracy (MHG vs. others), the techniques were XGBoost tree (100%); random trees (99.9%); random forest (99.5%); and C5, Bayesian network, SVM, logistic regression, KNN algorithm, neural networks, LSVM, discriminant analysis, CHAID, C&R tree, tree-AS, Quest, and XGBoost linear (99.4–91.1%). The inputs (predictors) were all the genes of the array and a set of 28 genes related to DLBCL-Burkitt differential expression. In summary, artificial intelligence (AI) is a useful tool for predictive analytics using gene expression data.