Background: Previous studies have shown that prognosis in metastatic colorectal cancer (mCRC) may vary according to sites of metastasis. We evaluated prognosis in individuals with single site metastasis, according to several clinical and genetic variables. Methods: Using the National Cancer Database we identified 58,044 mCRC patients with a synchronous single site of metastasis. We first examined the effect of metastasis site on prognosis. In a secondary analysis, among individuals who had not undergone surgery or received radiotherapy, we examined the prognostic value of chemotherapy intensity, KRAS status, primary tumor location and CEA levels. Results: Individuals with lung metastasis had the best prognosis (HR = 0.80, 0.77-0.83), followed by those with liver metastasis (HR = 1.11, 1.07-1.15), while those with bone or brain metastasis had the worse prognosis. In a subgroup analysis, we assessed prognosis among individuals who received multi-agent chemotherapy and had not undergone surgery or received radiotherapy. Individuals with lung metastasis and mutant KRAS had better prognosis compared with those with liver metastasis, (HR = 0.69, 0.54-0.88), regardless of primary tumor location or CEA levels. Conclusions: Single site metastasis to the lungs is associated with better prognosis in mCRC, specifically among KRAS mutant tumors. This survival advantage should be taken into consideration in clinical decision-making.