Background: Previous studies have shown that prognosis in metastatic colorectal cancer (mCRC) might vary according to sites of metastasis. We evaluated prognosis in individuals with mCRC and single-site metastasis, according to several clinical and genetic variables. Patients and 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, Kirsten ras (KRAS) status, primary tumor location and carcinoembryonic antigen (CEA) levels. Results: Individuals with lung metastasis had the best prognosis (hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.77-0.83), followed by those with liver metastasis (HR, 1.11; 95% CI, 1.07-1.15), whereas those with bone or brain metastasis had the worse prognosis. In a subgroup analysis, we assessed prognosis among individuals who received multiagent 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; 95% CI, 0.54-0.88), regardless of primary tumor location or CEA levels. Conclusion: Single-site metastasis to the lungs is associated with better prognosis in mCRC, specifically among patients with KRAS mutant tumors.