Approximately 20% to 25% of patients with colorectal cancer (CRC) have distant organ metastasis at the time of initial diagnosis. The primary tumor location has been suggested as a prognostic factor for patients with metastatic CRC. In recent years, the distinction between right colon cancer (RCC) and left colon cancer (LCC) has been brought into focus due to their different outcomes, prognoses, and clinical responses to chemotherapy. In this article we aimed to review the underlying differences between metastatic RCC and LCC in terms of epidemiology, clinical features, and oncologic outcomes. The outcomes of patients with left-sided tumors were better than those of patients with right-sided tumors in terms of overall survival (OS) and objective response rate (ORR) after treatment with chemotherapy + panitumumab in the PRIME and 20050181 trials. The outcomes of patients with LCC were better than those of patients with RCC in terms of OS, progression-free survival (PFS) and ORR after treatment with FOLFIRI + cetuximab in the CRYSTAL and CALGB 80405 trials. In the FIRE-3 trial, the OS and PFS, but not the ORR, of patients with LCC were superior to those of patients with RCC. LCC and RCC exhibit distinctive clinical features and epidemiology. However, we must further investigate the impact of these distinctive features and how they influence the differential oncologic outcomes.