Although immune-checkpoint inhibitors (ICIs) have become an important choice of treatment for advanced NSCLC, recent reports show hyperprogressive disease (HPD) after ICI administration. The clinico-pathological features of HPD still remain unclear. Here we report a 65-year-old man with lung adenocarcinoma who abruptly presented HPD two days after pembrolizumab administration. The primary tumor increased in size from 40 mm to 57 mm on the chest HRCT. The patient died on day 37 after pembrolizumab administration. The autopsy demonstrated widespread progression of cancer cells into the alveolar spaces and lymphangitic carcinomatosis in the left lung, with plenty of bloody pleural effusion. We compared the pathohistology and immunohistochemical expression of PD-L1 between the pretreatment biopsy material and posttreatment autopsy materials, and found a change in PD-L1 expression which may be related to HPD. We also discuss the possibility of HPD, pseudoprogression, and interstitial lung disease when there is evidence of tumor growth or ground glass shadows on chest images after ICI treatment.