Kagimoto A, Tsutani Y, Kushitani K, et al. - Whether S100 calcium-binding protein A4 (S100A4: a member of the S100 family of proteins and is a known marker of tissue fibrosis) can serve as a beneficial tool to predict acute exacerbation (AE) of interstitial pneumonia (IP) following lung resection for lung cancer, was investigated herein. Participants were 162 patients with IP findings on preoperative high-resolution computed tomography scan who had curative-intent lung resection for primary lung cancer between April 2007 and March 2019. Serum S100A4 generated receiver operating characteristic area under the curve of 0.871 for predicting postoperative AE of IP, yielding a sensitivity of 93.8% and a specificity of 75.3% at the cutoff value of 17.13 ng/mL. In multivariable analysis, a significant risk for AE of IP was shown to be conferred by a high serum S100A4 level (> 17.13 ng/mL). Patients with high serum levels of S100A4 were found to have significantly shorter 1-year overall survival when compared with patients with low serum levels. Overall, findings demonstrate a high predictive value of serum S100A4 for postoperative AE of IP as well as short-term mortality post-lung resection.