A 71-year-old woman presented with nodules in the right and left upper lung lobes with left pleural effusion. Pleural effusion cytology revealed adenocarcinoma. The left upper lung lobe adenocarcinoma was cT1aN0M1a (PLE) stage IVA and EGFR mutation-positive (exon 19 deletion). Afatinib treatment reduced the left upper lobe nodule and left pleural effusion. However, the right upper lobe nodule increased, and liver metastasis occurred. Histopathologically, the liver biopsy revealed metastasis from lung adenocarcinoma with more poorly differentiated malignant cells than those observed on pleural effusion cytology. The tumor showed high levels of PD-L1. EGFR mutation was not detected. After cytotoxic anticancer drug treatment, pembrolizumab treatment reduced the right upper lobe nodule and liver metastasis. However, the pleural effusion increased again. After cytotoxic anticancer drug treatment, afatinib treatment reduced the left pleural effusion.