CA19-9 is a specific tumor marker in patients with gastrointestinal cancer; however, some patients with respiratory disease can have elevated serum levels of CA19-9 as well. In this study we evaluated serum CA19-9 levels of patients with nonmalignant respiratory diseases. We also estimated the prognostic significance of elevated serum levels of CA19-9 in patients with interstitial lung diseases. The study included 554 patients who had been diagnosed at our hospital during the period of 1984-2005. Serum CA19-9 levels in these patients were measured with a commercially available kit. Elevated levels (437 U/mL) of CA19-9 were observed in 30.7% of patients with lung cancer. Furthermore, 38.9% of patients with idiopathic interstitial pneumonia (IIP), collagen disease-associated pulmonary fibrosis (CDPF), diffuse panbronchiolitis (DPB), and bronchiectasis had elevated serum CA19-9 levels. Survival rates were significantly lower in patients with interstitial lung diseases (IIP and CDPF) and elevated serum CA19-9 levels than in those with levels in the normal range (P 5 0.0065). Serum CA19-9 was elevated in some patients with nonmalignant diffuse lung diseases. Therefore, clinicians should pay attention to the evidence that increased serum CA19-9 levels can be found in nonmalignant respiratory disease patients. In patients with IIP and CDPF, elevated serum CA19-9 levels may be related to poor prognosis.