A 36-year-old woman had undergone left radical nephrectomy followed by interferon-α and sunitinib for the treatment of renal cell carcinoma with para-aortic lymph node and lung involvements (papillary renal cell carcinoma, G3, cT3aN1M1) in the previous hospital. She was referred to our hospital for further treatment and received serial molecular targeted agents (everolimus, sorafenib, sunitinib) and radiation therapy for right ischial and femoral bone metastases. Then she was found to have multiple metastatic lesions in the lungs and carcinomatous pleural effusion associated with dyspnea. After failure of pleurosclerosis with OK-432, the pleural effusion markedly reduced by axitinib administration, but the pleural effusion relapsed a few days after axitinib was discontinued. For this reason, axitinib was maintained in spite of appearance of new metastatic lesions in the brain. The pleural effusion was well-controlled for 16 months but she died of progressive disease, including metastatic lesions in the brain and in the lungs.