A 66-year-old female patient underwent left upper lobectomy and dissection of the mediastinal lymph nodes. The pathological diagnosis was well-differentiated papillary adenocarcinoma of the lung with metastasis to the mediastinal lymph nodes, p-T2N2MO, stage IIIA. After the operation, she was treated by chemotherapy including lipophilic anticancer compounds (carboplatin and VP-16). The patient unexpectedly showed long survival for 6 years and 2 months without obvious recurrence or metastasis of the cancer. The anticancer compounds were not effective on the recurrent lesions and then she died due to respiratory failure 8 months after recurrence. The autopsy revealed pleural dissemination and intrapulmonary metastasis. Immunohistochemical analysis showed increased multidrug resistance-associated protein (MRP)-positive tumor cells in the recurrent and metastatic lesions, while few MRP-positive cells were apparent in the primary lesion. The MRP-positive cells were accompanied by p53 nuclear accumulation in the carcinoma. This was a case of pulmonary adenocarcinoma with acquired multidrug resistance caused by MRP overexpression and aberrant p53 after chemotherapy.