Although Zhao et al. argue that RSPO1 treatment can reduce the tumorigenic risk by decreasing inflammation in inflammatory bowel disease (Zhao et al., 2007), several authors suggest that aberrant Wnt pathway signaling, especially hyperactivation, is strongly associated with the presence of various types of cancer in humans and mice, including colon cancer (Yoon and Lee, 2012). This evidence concerns the gene RSPO1 and inflammatory bowel disease.