The planktonic genus Planktothrix, as other cyanobacteria, shows signals of both homologous and nonhomologous recombination. However, the frequency of recombination and its effect on Planktothrix population structuring is unknown. We isolated 290 Planktothrix strains from seven neighboring lakes in the subalpine Italian region and analyzed these using multilocus sequence typing. Four of six loci analyzed were polymorphic, resulting in 20 distinct multilocus genotypes. Association indices among alleles at different loci were suggestive of an “epidemic population structure,” resulting from an explosive (and temporary) dominance of one genotype against a panmictic background. ClonalFrame analyses supported this view by detecting: (i) three major clades affected by three distinct recombination events, (ii) a recombination rate about equal to the mutation rate, and (iii) the fact that recombination had an impact on introducing molecular diversity more than double the mutation rate. Furthermore, analysis of molecular variance over an annual cycle in three of seven lakes revealed that both local clonal expansion and recombination processes affected among-lake diversity. Our observations suggest that recombination affects microevolution of Planktothrix and that an epidemic structure can emerge in populations of this genus.