Ameloblastoma (AM) is most commonly encountered in the jaw bones. The etiopathogenesis is idiopathic. Keratocystic odontogenic tumor (KCOT) is controversially considered a cyst and a tumor. According to World Health Organization, KCOT is a benign, unicystic or multicystic, intraosseous tumor of odontogenic origin. Either syndromic or non-syndromic, the PTCH gene is proven participant in the etiology. This study contrasts the expression of AM and KCOT for CD44. CD44, a transmembrane glycoprotein, is a homing cell adhesion molecule and is a stem cell marker for breast, prostate, pancreatic cancers and for several head and neck benign and malignant tumors. The results show that KCOT demonstrates a stronger positivity than AM. In conclusion, the breakdown in the cellular adhesion, as a clue to osteoclastogenesis, is stronger in KCOT than in AM. The strong expression of KCOT for the monoclonal antibody of CD44 defies the cystic nature and supports the neoplaticity of KCOT.