Horizontal gene transfer (HGT) is one of the most interesting evolutionary events in Eukaryotic life. It has been proven that fungi share genes or gene clusters with other organisms such as plants, animals, or other fungi. The amatoxins biosynthesis metabolic pathway produces lethal bicyclic peptides responsible for most of the deaths by mushroom poisoning. It is assumed that involved genes passed from Galerina and Lepiota to the Amanita secc. Phalloidae species by HGT. We used de novo genome assembling and gene mining for homologous amanitin genes among Agaricomycetes lineages. Phylogenetic and reconciliation trees were constructed to address the evolutionary history of POP gene family responsible for amanitin maturation. We also looked for the potential cytotoxicity of sequenced samples on plant bioassays. New and known edible species in Amanita rubescens complex have, partially or completely, the gene’s package implied in the synthesis of amatoxins, making them potentially capable of synthesizing these lethal metabolites. The evolutionary history of these genes is more complex than previously reported involving at least ten HGT events, four duplication events, other fungal genera such as Piloderma and Russula, and several edible mushrooms. Furthermore, we showed that samples from a traditionally consumed species within Amanita rubescens complex had the same cytotoxicity capabilities as the lethal amanitas from the Phalloideae section. In conclusion, several old duplications and horizontal gene transfer events originated a cryptic diversity of the POP gene family in toxic and edible fungi raising questions on the safe consumption of species in the A. rubescens complex.