There has been a flurry of recent interest in the effect of primary tumor sidedness on prognosis and treatment response among patients with colorectal cancer (CRC). This interest has largely been sparked by recent observations that among patients with metastatic CRC (mCRC), primary tumor sidedness was associated not only with prognosis but also, among those patients without KRAS mutations, with response to epidermal growth factor receptor (EGFR).1,2 Based on these findings, a number of investigators now advocate for the inclusion of tumor sidedness as an important stratification criteria in the design of future clinical trials. Naturally, these observations have led many investigators to question if tumor sidedness is also prognostic in patients with localized disease.