The Euphorbiaceae family is renowned for its diverse array of compounds, primarily diterpenes, which exhibit multiple biological activities. In Brazil, the genera Jatropha, Cnidoscolus, Sapium, and Stillingia are predominantly found in the Northeast region. Despite their significant pharmacological potential, the chemical profiles of these species remain underexplored. In this context, chemotaxonomic is a tool to identify potential markers and bioactive structures within a given taxon. In order to analyze the chemical patterns among the diterpenes present in the four selected Euphorbiaceae genera, Phylogenetic Reconstruction and Self-Organizing Maps (SOMs) were applied. Two data sets were constructed: one containing 308 diterpenes structures and their 363 botanical occurrences, and a genetic data set encompassing ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) sequences of the selected species. The reconstruction exhibits a close relationship between Jatropha and Cnidoscolus, although it was not able to distinguish Sapium and Stillingia. In other hand, SOMs classified the diterpenes in two groups: the first containing benzene-derived compounds and the second encompassing mainly the tigliane-type, which stands out as a chemical signature. Both groups contain substances with significant cytotoxic activity. This study may guide the discovery of new cytotoxic compounds and provide new insights into the systematics of the Euphorbiaceae family.