Pulmonary pleomorphic carcinoma is refractory to chemotherapy and has a poor prognosis. A 54-year-old woman was referred to our hospital because of an abnormal shadow on her chest radiograph obtained during a physical examination. A systemic examination was performed, and pleomorphic carcinoma cStage ⅢA was diagnosed. A gene mutation search using biopsy specimens revealed that the EGFR exon 19 deletion mutation was positive and that PD-L1 (22C3 antibody) was highly expressed with a tumor proportion score (TPS) of >75%. Following chemoradiation therapy and 7 courses of durvalumab as maintenance therapy, the disease progressed. After carboplatin plus nab-paclitaxel as 2nd line therapy and osimertinib as 3rd line therapy, pembrolizumab as 4th line therapy was initiated. Marked tumor shrinkage was observed, and this partial response has been maintained for more than two years. In a case of EGFR-mutated pulmonary pleomorphic carcinoma, it is worth considering re-administration of immune checkpoint inhibitors based on PD-L1 expression status and the course of treatmen