SMYD3 methylates not only histone H3 at lysine 4 but also histone H3 at lysine 9, histone H4 at lysine 5, and histone H4 at lysine 20 [13, 18, 32]; these histone lysine methylation events meditated by the SET domain of SMYD3 exert significant effects on cancer development and progression. The gene discussed is SMYD3; the disease is cancer.