The goal of this study was to identify the optimal marker or marker combinations for detection of gastrointestinal malignancies using reverse-transcriptase polymerase chain (RT-PCR) reaction. To detect the presence of tumors, we analyzed mucin 1 (MUC1), cytokeratin 19 (CK19), cytokeratin 20 (CK20), and human telomerase reverse transcriptase (hTERT) mRNA in the peripheral blood of 31 patients with gastrointestinal (esophagus, stomach, and colorectal) cancer and 30 healthy individuals. In RT-PCR analysis of the peripheral blood, 77.4% (24/31), 61.29% (19/31), and 45.16% (14/31) of cancer patients were positive for MUC1, CK20, and hTERT mRNA, respectively. According to our results, any one of these mRNA markers is a predictor of the presence of gastrointestinal tumors (P < 0.001) and colorectal tumors (P < 0.05). However, they did not have predictive potential for presence of metastasis in gastrointestinal tumors. As a result, combination of these 3 tumor-specific mRNA markers would increase the detection rate and may be clinically helpful in predicting tumor presence.