We examined serial changes in serum CA19-9 levels in patients with pancreatic cancer (PC) or chronic pancreatitis (CP) to clarify whether these changes are useful in the diagnosis of PC. We chose II PC patients in whom serum CA19-9 levels had been measured serially before a definitive diagnosis of PC had been established. We also examined serial changes in serum CA19-9 levels during the recent 1-year follow-up period in 21 CP patients. Serial changes in these levels were classified into the following five types; normal, elevated, increased, decreased, and other. Of the 11 PC patients, seven patients (64%) showed the increased type, whereas none showed the normal type. However, among the CP patients, 10 patients (48%) showed the normal type and only one (5%) showed the increased type. The proportion of the increased type among PC patients was significantly higher than that among CP patients. In conclusion, serial changes in serum CA19-9 levels may be useful to differentiate between PC and CP. Close follow-up with various diagnostic modalities may be required for patients whose serum CA19-9 levels increase to more than twofold the initial level, because such findings are highly suggestive of PC.