Targeting well-recognized CD44 abnormal mechanism to block aberrantly activated signaling pathways in tumor cells by antibodies, peptides, aptamers, hyaluronic acid oligomers, or chemotherapy is a current priority, but to understand the precise regulatory role of CD44 intracellular domains in this complex activation of abnormal signaling pathways is beginning to be considered a priority. Here, CD44 is linked to neoplasm.