To investigate whether serum levels of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) were related to first stage cancer before diagnosis of cancer, we compared serum levels of these adhesion molecules between pre-clinical cases and controls using a nested case-control study method. Cancer cases were recruited from a cohort database of 1465 participants who completed a baseline questionnaire and provided blood samples, and were followed up from 1989 to 2003. They consisted of 15 individuals who died of cancer and 31 individuals newly diagnosed with cancer during the follow-up period. Controls were subjects who did not suffer from cancer, cerebral apoplexy, diabetes mellitus, liver disease, or myocardial infarction during the follow-up period. Using commercially available enzyme-linked immunosorbent assay (ELISA) kits, we showed that serum levels of sVCAM-1, but not sICAM-1 were elevated in cases with pre-clinical or early cancer. We suggest that elevated serum levels of sVCAM-1 might serve as a possible marker for detecting pre-clinical or early cancer.