Cyanobacteria are photosynthetic prokaryotes that are able to synthetize a wild rang of secondary metabolites exhibiting noticeable bioactivity, comprising toxicity. Microcystis represents one of the most common cyanobacteria taxa constituting the intensive blooms that arise nowadays in freshwater ecosystems worldwide. They produce numerous cyanotoxins (toxic metabolites), which are potentially harmful to Human health and aquatic organisms. In order to better understand the variations in cyanotoxins production between clones of the same blooms, we investigate the diversity of several Microcystis strains isolated from different freshwater bloom-forming populations from various geographical area. Twenty-four clonal strains were compared by genotyping with 16S-ITS fragment sequencing and metabolites chemotyping using LC ESI-qTOF mass spectrometry. While, genotyping can only discriminate between the different species, the global metabolomes reveal clear discriminant molecular profiles between strains, which can be clustered primarily according to their global metabolite content, then to their genotype, and finally to their sampling localities. A global molecular network generated from MS/MS fractionation patterns of the various metabolite detected in all strains performed with GNPS tool highlight the production of a wide set of chemically diverse metabolites, comprising only few microcystins, but many aeruginosins, cyanopeptolins and microginins, along with a large set of unknown molecules that still remain to be investigated and characterized at their structure as well as at their potential bioactivity or toxicity levels. Figure 1: Microcystis spp. General view of a representative intense Microcystis sp. bloom in a recreational pound (Champs-sur-Marne) (A). Macrograph of Microcystis colonies at surface water (B). Example of 15-mL vessels containing the monoclonal strains of Microcystis spp. maintained in the Paris' Museum Collection (PMC) of cyanobacteria (MNHN, Paris) (C). Example of micrograph of the isolated monoclonal culture of the Microcystis aeruginosa, where scale bare represents 10 µm (D). Representative picture of Microcystis aeruginosa cell from PMC 156.02 strain (here in division) under transmission electron microscope, where scale bare represents 0.5 µm (E). General structures of various cyanobacterial metabolites belonging to the microcystin, anabaenopeptin, microginin microviridin, aeruginosin and oscillatorin families (F).Microcystis wesenbergii PMC 672.10 84 Microcystis wesenbergii PMC 671.10 Microcystis wesenbergii PMC 673.10 Microcystis wesenbergii PMC 674.10 Microcystis wesenbergii NIES111 (3551457) (AB015388) Microcystis wesenbergii TAC52 (3551459) (AB015390) Microcystis sp. PMC 807.12 Microcystis viridis PMC 566.08 88 Microcystis wesenbergii NIES44 (3551456) (AB015387) Microcystis viridis TAC17 (3551467) (AB015398) Microcystis viridis W191 (295983850) (HM017091) Microcystis viridis W18 (295983846) (HM017087) Microcystis aeruginosa PMC 265.05 Microcystis sp. PMC 816.12 Microcystis aeruginosa PMC...