Here we present a case in which alternation of interferon-alpha (IFN-alpha) treatments was effective in treating pulmonary metastases and lymph node metastases from renal cell carcinoma (RCC). A 56-year-old man underwent left radical nephrectomy under the diagnosis of left RCC. The histological diagnosis was clear cell carcinoma G2, IFN-alpha, pT1b. He subsequently underwent two operations for right pulmonary metastasis and right hilar lymph node metastasis. Postoperatively he was treated with intramuscular administration of natural IFN-alpha (Sumiferon) which prevented definite recurrence for 1 year. However, multiple pulmonary metastases and left hilar lymph node metastasis occurred 11 months after discontinuation of Sumiferon. Therefore, treatment with another natural IFN-alpha (OIF) was started. Although OIF was continued for 7 months, pulmonary metastases and left hilar lymph node metastasis continued to progress. Therefore, treatment was changed to Sumiferon, after which the pulmonary metastases and left hilar lymph node metastasis decreased in size. The metastases showed no progression for 16 months after switching from OIF to Sumiferon.