A case of pyonephrosis with high levels of serum CA19-9 antigen is reported. A 71-year-old woman was admitted with right flank pain. Computed tomography and ultrasonography showed severe hydronephrosis and hydroureter due to a right ureter stone. Laboratory data revealed a high level of serum CA19-9. However, no tumor was found in the pancreas, gallbladder, liver, gastrointenstinal tract or genitourinary tract. Drip infusion pyelography showed a non-functioning pattern of right kidney. Therefore, right nephroureterectomy was performed for right pyonephrosis. Histological examination revealed chronic inflammation. Malignant cells were not seen in the resected specimen. The serum CA19-9 levels before and after operation were 102.9 U/ml and 24 U/ml, respectively, being normal after the operation. Immunohistochemical examination revealed the presence of CA19-9 antigen in the urethelium, indicating its expression in the specimen. To our knowledge this might be the first case of pyonephrosis associated with high levels of serum CA19-9 antigen.