The alteration of cellular metabolism has been recently recognized as a hallmark of cancer.1 Central to the metabolic reprogramming of cancer cells are the complex pathways involving folates, providing the essential precursors to sustain cancer cell growth and affecting cellular antioxidative and methylation capacities, thus supporting tumor homeostasis.2 Serine hydroxymethyltransferase (SHMT) is a key protein in this scenario: its main function is to catalyze the folate-dependent serine/glycine interconversion. This evidence concerns the gene SHMT1 and cancer.