Background: Over the past 35 years, there has been a significant increase in the number of patients below the recommended initial screening age (50 years old) diagnosed with colorectal cancer (CRC). Early onset colorectal cancer is more likely to occur in non-white patients, be located in the rectum, be diagnosed at a more advanced stage, and have concerning pathological features. The immune microenvironment in CRC is a key player in disease progression, therapy response, and overall survival. However, the role of the immune microenvironment in early onset CRC, particularly in rectal cancer has not been investigated. This study aims to characterize the immune microenvironment of early onset ( 50 years old) and late onset ( 65 years old) colon and rectal cancer patients. Methods: We used Nanostring immune profiling to analyze FFPE surgical specimens and identified genes that were differentially expressed between early and late onset colon and rectal cancer groups. We validate our results with qPCR. The differentially expressed genes in the rectal cancer cohort were compared to our analysis of a publically available database (GSE8721) of gene expression profiles for 203 rectal cancer and 160 matched normal mucosa samples. Immunohistochemistry (IHC) was performed on FFPE colorectal specimens for CXCL3. Results: Using Nanostring, we identified two genes that were differentially expressed between early and late onset colon cancer (IFITM1, CXCL3) and two genes in the rectal cancer cohort (FLT3, SAA1). CXCL3 has increased expression in late onset colon cancer utilizing qPCR and IHC. High expression of CXCL3 in both IHC and qPCR is associated with improved disease free survival. Analysis of the GSE8721 database also showed that FLT3 and SAA1 were differentially expressed in early versus late onset rectal cancer. Using qPCR, FLT3 is increased in early onset rectal cancer specimens compare to late onset rectal cancer, early and late onset colon cancer, and normal colon. Conclusions: There are distinct differences in the immune microenvironment between early and late onset colon and rectal cancer that may hold the potential for targeted therapeutics.