The squamous cell carcinoma antigen (SCC-Ag) has been widely applied as a serum marker in different kinds of cancer and was reported as a target gene for the detection of tumor cells in peripheral blood in cervical cancer. Nucleic acids released into the circulation are non-invasive diagnostic tools for cancer detection. The objective of this study was to determine the utility of SCC-Ag mRNA as a cancer detection marker in blood of cancer patients. For this purpose, 77 blood samples from five gastric cancer, 23 laryngeal cancer, 31 lung cancer, nine esophageal, and nine cervical cancer patients were analyzed. The SCC gene was amplified by reverse transcription-polymerase chain reaction. SCC-Ag mRNA was detected in two patients with gastric cancer, six patients with laryngeal cancer, 17 patients with lung cancer, three patients with esophageal cancer, and two patients with cervix cancer. The detection rate was highest (54.83%) in patients with lung cancer. SCC-Ag transcripts were not detectable in the control group, indicating that molecular analysis showed no false positives. Our results indicate that this approach could be useful in a considerable number of patients and could improve the lower diagnostic yield of conventional tests.