Dramatic differences in chromosome number within clades are often interpreted as being due to polyploidy. Such chromosomal changes have in fact have been used to infer a high frequency of polyploidy in certain taxonomic groups, such as the angiosperms. Phylogenetic analysis of chromosome number differences among monkeyflowers in the genus Mimulus had implicated multiple polyploidy events in different lineages in raising the basal number from n=8 to n=14 or 16. The recent sequencing and assembly of the Mimulus guttatus genome (n=14), together with the availability of large numbers of transcript sequences from M. lewisii (n=8) allows us to test this hypothesis. Based on phylogenetic and clock-based dating of paralogs in duplicated chromosomal regions within M. guttatus, we detect two large-scale duplication, and presumably polyploidy, events. The older of these two is inferred to be a hexaploidy event shared across all eudicots. The younger is likely a tetraploidy event dating to 46-70 MYA, prior to the divergence of the two Mimulus species examined here (but postdating divergence with the Solanaceae lineage). Thus, remarkably, approximate chromosome doubling in Mimulus appears to have accomplished through multiple chromosomal fission events clustered in time.