The almost ten times higher numbers of spontaneous lung metastasis found in pfp/rag2 mice in comparison to 3 times higher numbers of circulating tumor cells in the bloodstream of pfp/rag2 mice indicate that perforin dependent direct cytotoxicity of NK cells reduces the number of malignant cells significantly in both the bloodstream and the connective tissue stroma in the distant organ. The gene discussed is RAG2; the disease is neoplasm.