BACKGROUND Sialyl Lewis X-i antigen has been used as a diagnostic tool for lung adenocarcinoma. However, serum levels of the antigen are also raised in some patients with idiopathic pulmonary fibrosis (IPF) without coexistent malignancy. Expression of the antigen in serum samples of patients with lung adenocarcinoma was evaluated and compared with that of patients with IPF by Western blotting in order to establish a specific laboratory test to differentiate lung adenocarcinoma from IPF. METHODS The pattern of antigen expression in serum samples from 23 patients with either lung adenocarcinoma or non-malignant lung disease in whom serum levels of sialyl Lewis X-i antigen (>50 U/ml) were significantly increased was studied by Western blotting. RESULTS Thirteen of the 14 serum samples from patients with lung adenocarcinoma had a molecular weight band at 120 or 130 kD, while five of the six patients with IPF had two or three bands at <97.4 kD. The pattern of antigen expression was apparently different between the two diseases. The sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of this test in 20 patients with lung adenocarcinoma and IPF were 92.9%, 83.3%, 5.57, and 0.09, respectively. CONCLUSIONS Western blotting analysis of serum samples from patients with raised levels of sialyl Lewis X-i antigen provides some clinical information for a differential diagnosis between lung adenocarcinoma and IPF.