Our preclinical results as well as the recent study of Kakugawa et al. [4] and the comments of Nusse [14], describing the mechanism by which Wnt signals can be down-regulated by the extracellular enzyme Notum in Drosophila, prompted us to investigate Notum and glypican levels in a set of human CRC samples. This evidence concerns the gene GPC1 and colorectal carcinoma.