Histone methyl marks orchestrate programming of the genome, regulating gene expression programs that control growth, survival and differentiation in response to changing environmental cues. Thus, the discovery and functional characterization of new histone methylation marks holds great promise in expanding our understanding of how chromatin dynamics influence genomic programs. Characterization of evolutionarily conserved histone methylation sites in Saccharomces cereviaise has provided essential insight into the function of post translation modification in diverse eukaryotic systems, including humans. Taking advantage of the versatile molecular genetic tools available in yeast, we have investigated the biochemical and biological roles of the novel candidate histone methyltransferase, Set6, whose function is not known. Set6 contains a SET domain, a common signature of chromatin regulatory proteins that catalyzes lysine methylation. Here, we use genetic assays to show that Set6 participates in cell cycle regulation, and may specifically be important for progression through S phase. We further use biochemical approaches to demonstrate that Set6 is likely an active methyltransferase that may primarily target non-histone proteins. Overall, we hypothesize that Set6 is a key regulator of cell cycle progression in budding yeast that acts via its methylation activity on non-histone proteins.