Colorectal carcinoma (CRC) is the third most common cancer type in the United States . While the incidence of CRC is decreasing among an older population undergoing screening, the incidence of early-onset CRC is rising . There is a growing understanding that the molecular underpinnings of colorectal carcinoma vary by age . In this study we report the genetic alterations and clinicopathologic features of a single-institution colorectal carcinoma cohort over a 2-year period using a next generation sequencing (NGS) approach and microsatellite stability (MS) status determined by immunohistochemical staining . 40 cases were identified in an early-onset cohort (eCRC) defined by age <40 years and 164 cases were identified in age-related cohort (arCRC) defined by age> 70 years . eCRC was more often-left-sided/rectal and more likely to present high rates of lymph node positivity with metastatic disease . NGS mutational analysis revealed distinct differences between eCRC and arCRC, with eCRC being characterized by low frequency of PIK3CA mutations, elevated frequency of KRAS and CTNNB1 mutations in MSI-H tumors, and very low frequency of BRAF mutations.