We devoted this short piece to highlight one recent article published in Science, which revisited the anti-cancer efficacy of high-dose vitamin C. Using isogeneic KRAS-and BRAF-mutated colorectal cell lines, the authors were able to demonstrate selective antitumor effects among the KRAS-and BRAF-mutated cells in culture and in ex-planted animal models treated with high-dose vitamin C. Their elegant and in-depth studies unequivocally tied the tumoricidal effect to the heightened sensitivity of the mutant cells due to the increased vitamin C uptake, leading to lethal accumulation of reactive oxygen species (ROS). This report will certainly rekindle enthusiasm in revisiting the case of vitamin C, pushing for more definitive cancer therapy trials.