The present study is designed to evaluate the use of the tumor marker Tumor M2-PK in the discrimination between gastrointestinal (Gl) cancer patients and patients with non malignant gastrointestinal diseases. The concentration of Tumor M2-PK was analyzed in EDTA-plasma of 413 Gl cancer-patients and 141 patients with non-malignant diseases. The test resulted in a highly significant discrimination (p < 0.001) of tumor patients and controls. The diagnostic specificity was 89%. A diagnostic sensitivity between 48% and 73%, depending on the different tumor entities (colorectal cancer, gastric cancer, oesophageal cancer and pancreatic cancer), was observed. These sensitivities were generally higher when compared with those of the established tumor markers CEA, CA 19-9 and CA 72-4, with the exception of CA 19-9 in pancreatic cancer. A combination of Tumor M2-PK with the appropriate first choice-marker (e.g. CEA + Tumor M2-PK for colorectal cancer) resulted in a remarkable increase in the sensitivities.