Background: CA 19-9 is a useful marker for the diagnosis of gastrointestinal cancer including pancreatic cancer. However, there are several previous studies about CA 19-9 elevation in benign lung diseases like emphysema, fibrosis and bronchiectasis. This study investigated the clinical significance of serum CA 19-9 elevation in pulmonary nontuberculous mycobacterial (PNTM) disease, compared with pulmonary TB. Method: Serum CA 19-9 in patients with PNTM (n=59) and pulmonary TB (n=36) were measured. Multivariate logistic regression analysis was performed to evaluate the factors related to CA 19-9 elevation in PNTM disease. The sequential changes in serum CA 19-9 before and after treatment were compared between pulmonary TB and PNTM disease. Results: The median CA 19-9 level was higher in patients with PNTM disease than pulmonary TB (PNTM: 13.80, TB: 5.85, P＜0.001). However, after adjusting for age, sex, radiologic severity and previous TB history, the CA 19-9 levels between two groups were not different (PNTM: 28.35, TB: 12.68, P =0.471). Among 59 patients with PNTM disease, serum CA 19-9 levels were elevated in 11(18.6%). M.abscessus species (OR 10.37, 95% CI: 1.96, 54.93; P=0.006) and extensive pulmonary lesions more than three lobes (OR 6.37, 95% CI: 1.02, 39.60, P=0.047) were significantly associated with an elevated CA 19-9 levels. While the CA 19-9 levels showed a tendency to decrease during successful treatment of PNTM disease, but not in pulmonary TB. Conclusions: Serum CA 19-9 level was increased in substantial proportions of the patients with PNTM disease and it may be useful in the monitoring of therapeutic responses of PNTM disease.