Dipeptidyl peptidase IV (DPPIV/CD26) is a multifunctional protein with intrinsic peptidase activity that inactivates or degrades some bioactive peptides. It is the main cellular binding protein for ecto-adenosine deaminase and interacts with extracellular matrix proteins, besides participating in different signaling pathways. Due to these multiple functions, DPPIV/CD26 has been shown to be closely related to the tumor process. It has been reported that the progression of certain types of cancer is accompanied by a decrease in DPPIV/CD26 expression, and studies have shown that the malignant phenotype can be reverted when DPPIV/CD26 expression is induced in these cancer cells, characterizing this protein as a tumor suppressor. On the other hand, DPPIV/CD26 was described as a protein associated with invasion and metastatic spread, characterizing it as a marker of malignancy. Thus, this review explores the roles of DPPIV/CD26 expression in tumor progression in different types of cancer and demonstrates the importance of this protein as a promising therapeutic target and tumor biomarker.