Various investigation has shown the magnitude role of adenosine receptors in cancer development. The A1, A2A, A2B, and A3 G-protein-coupled cell surface Adenosine Receptors (ARs) are found to be upregulated in many types of cancers. The adenosine receptor function has been affected by specific ligands such as agonists and/or antagonists regulated cancer (Neoplasms) cells proliferation via signaling pathways. Adenosine not only is an important intermediate metabolite but also acts as the essential ligand of adenosine receptors in physiological and pathological conditions. Furthermore, many studies have shown that adenosine receptors expression has increased in many types of cancer. In this review, we first describe adenosine's role in physiological condition and in cancer development. We further, discuss the type of adenosine receptors, distribution, expression, and their roles in cancer.