CD44 variable alternative exon 6 (CD44 V6) is a variant isoform of the CD44 gene resulting from alternative splicing of RNA. CD44 is a cell adhesion molecule that is present in various cell types and plays crucial roles in biological processes such as cell migration, proliferation, and differentiation. The CD44 V6 isoform specifically, has been implicated in tumor development and metastasis. Research has shown that CD44v6 is expressed by all colorectal cancer stem cells (CR-CSCs). The expression of CD44v6 is essential for the migration and formation of metastatic tumors, achieved through the activation of the WNT-β-catenin signaling pathway. Propelling evidence recommends that CD44v6 compared to CD44 has a more specific expression in CSCs and may have a higher diagnostic value.