Various tumor markers for detection of small pancreatic cancer less than 4.0 cm of diameter were evaluated and our recent 2 year experience is presented. Even in T1 cancer, 62.5% of the patients (N = 24) had elevated serum CA 19-9 and 56.5% of the patients also had elevated serum SPan-1. However, that of other markers was less than 30% except for CA 50 (60%). In T2 cancer, the highest sensitivity was observed for SPan-1 (79.6%, N = 54) and that of Ca 19-9 (N = 54) was also high (77.7%). That of other markers was less than 50%. The combination assay of CA 19-9 and SPan-1 in T1 cancer increased sensitivity from a single assay of 62.5% and 56.5%, respectively, to 70%. In T2 cancer, the sensitivity of the combination was 97.1%. All of our cases showed positive results using serum SPan-1 and/or CA 19-9 before confirming the diagnosis with imaging procedures. By applying measurements accurately, the test is a very useful adjunct to the diagnosis of small pancreatic cancer and therefore improves its prognosis.