Adenosine inhibits the immune response in tumors. Adenosine deaminase (ADA) controls adenosine level and as ecto-enzyme acts as costimulatory molecule of adenosine receptors and/or CD26. We examined ADA₁, ADA₂, ADA₆ polymorphic sites of ADA gene in 109 subjects with colon cancer from Rome's population and in 246 blood donors as controls from the same population. In colon cancer ADA₁*2/ADA₂*1 haplotype is more represented, while ADA₁*2/ADA₂*2 is less represented than in controls. ADA₂*2/ADA₆*2 is less represented in patients than in controls. Polymorphic sites of ADA might influence cell-mediated anti-tumor immune responses controlling adenosine level and extraenzymatic protein functions.