In recent years, protein methylation has been established as a major intracellular post‑translational modification (PTM). Over twenty protein methyltransferases have been identified in Saccharomyces cerevisiae that target histone and non‑histone substrates such as RNA‑binding proteins, elongation factors and ribosomal subunits. The question remains as to how these enzymes are regulated. We overexpressed and purified six Saccharomyces cerevisiae protein methyltransferases (Hmt1, Rkm1, Rkm3, Rkm4, Set5, Efm7) in their native host and subjected them to digestion by either trypsin or LysargiNase, followed by analysis with either LC‑HCD‑MS/MS or LC‑ETD‑MS/MS. Additionally, undigested samples were analysed via top‑down mass spectrometry with FT‑ICR MS to investigate the co‑occurrence of PTMs and the modform distribution of protein methyltransferases. This multi‑protease, multi‑fragmentation approach revealed a range of PTMs on several protein methyltransferases including phosphorylation, acetylation and methylation. Of particular interest is a range of PTMs on Rkm1, Set5, and the N-terminal tail of Hmt1. The N-terminal tail of Hmt1 has been shown to be implicated in modulating its oligomerisation state, which in turn regulates its activity. The close proximity of certain PTMs on Hmt1 and Set5 also raises the possibility of crosstalk between PTM pairs. In summary, the identification of several PTMs on protein methyltransferases suggests at least some methyltransferases are regulated post‑translationally and are end points of signalling pathways.