In summary, tumor cells respond to S100A9 better than S100A8, and its interaction with RAGE triggers different signaling pathways in favor of inflammatory tumor microenvironment, including Smad, NF-κB, MAPK/ERK, and SAPK/JNK and P38, leading to leukocyte recruitment angiogenesis, tumor migration, wound healing, and premetastatic niches. This evidence concerns the gene S100A9 and neoplasm.