This study investigated the immunohistochemical staining characteristics of human beta defensin-3 (hBD-3) and human cationic antimicrobial peptide-18/cathelicidin (hCAP-18/LL-37) in colon, stomach and lung adenocarcinomas and normal tissues (periphery to tumor tissues) from 22, 24 and 24 patients, respectively. Expressions of hBD-3 and hCAP-18/LL-37 were assessed by immunohistochemistry for colon, stomach and lung adenocarcinomas of 70 patients from Ataturk Chest Diseases and Thoracic Surgery Training and Research Hospital and Kecioren Training and Research Hospital. both located in Ankara, Turkey. The differences between the expressions of hBD-3 and hCAP-18/LL-37 in normal and carcinoma tissues were analyzed by Mann-Whitney U Test. When the normal and tumor tissues of these cases were compared according to their staining intensity of positive staining, the hBD-3 and hCAP-18/LL-37 expressions in colon, stomach and lung adenocarcinomas cells were significantly higher than those in normal cells (p<0.05). Immunostaining of HBD-3 and hCAP-18/LL-37 was found to be a marker of malignancy in colon, stomach and lung adenocarcinomas. The expressions of hBD-3 and hCAP-18/LL-37 were, for the first time, shown to be significantly altered in colon, stomach and lung adenocarcinomas as compared to controls. In conclusion, the present findings suggest that beside the antimicrobial activity of Antimicrobial Peptides (AMPs), hBD-3 and hCAP-18/LL-37 can also play a role in the pathogenesis of colon, stomach and lung adenocarcinomas.