A 57-year-old man with advanced EGFR mutation-positive (exon 19 deletion) adenocarcinoma (cT4N3M1b, OSS, HEP, LYM) of the right lung received first-line chemotherapy with gefitinib. On the first day of gefitinib administration, he suffered from constructive apraxia and a skill movement disorder. Brain MRI (diffusion-weighted image: DWI) showed multiple high-intensity signals in the right subcortical area. Despite the presence of hypercoagulation, neither arteriosclerosis nor vegetation was found. Therefore he was diagnosed as having Trousseau syndrome associated with primary lung cancer. He received anticoagulation with heparin and edaravone for Trousseau syndrome and also gefitinib for lung cancer. Both lung cancer and neurological symptoms with hypercoagulation status had improved after the therapy. Here we report the first case of advanced EGFR mutation-positive lung cancer with Trousseau syndrome successfully treated with first-line gefitinib.