The aim of this study was to investigate the expression of the SIGLEC9 protein in CRC tissues concerning the mutations in the KRAS, NRAS, BRAF, PIK3CA, and AKT genes, microsatellite instability (MSI) status, and the expression of cytokines, chemokines, and growth factors within the CRC TME. This evidence concerns the gene PIK3CA and colorectal carcinoma.