Mesothelin (MSLN) is a membrane bound protein that can promote survival, proliferation and invasion of cancer cells. Our previous work had shown a significant association between MSLN expression on resected localized CRC (Stage I-III) and future development of peritoneal carcinomatosis (PC) (p < 0.001). MSLN expression in early stage CRC was also associated with an inferior overall survival. We expanded this work by examining an additional cohort of patients at West Virginia University (WVU), WV, USA. This is a retrospective study of patients with localized CRC who underwent surgical resection from 2005-2019 at WVU. The patients were categorized into two groups based on whether they had a recurrence. Metastatic group comprised of patients who recurred and control group constituted patients who did not have a recurrence after a minimum of 5 years of surveillance. Metastatic group is further subdivided into 2 subgroups; SOM: patients who developed metastases in solid organs only; PC group: patients who developed PC at any time. MSLN staining with immunohistochemistry was performed using Rockland (MN1) mouse monoclonal antibody and scored based on intensity (0, 1+, 2+, and 3+) and percent positivity (0: 50%). MSLN total score was defined as the sum of intensity and percent positivity, with a total score of 3 or greater considered “positive” for MSLN expression. Fisher’s exact test was performed to determine the association of MSLN score and future recurrence of CRC. Out of a total of 484 patients diagnosed with localized CRC, 88 patients had a recurrence. Out of 88 patients, SOM and PC groups comprised 48 (54%) and 19 (22%) patients respectively while 21 patients (24%) had local recurrence. Control group comprised 126 patients. MSLN staining was completed on 70 patients in the entire cohort and the results are presented here. Among 70 patients, 14 patients had a recurrence in either solid organs (n-9) or peritoneum (n-5) and 56 patients did not recur. Positive MSLN score was demonstrated on resected CRC tissues in 8 out of 14 patients who had a recurrence; Five of them from the SOM group (5 out of 9 patients (55.6%)) and 3 from the PC group (3 out of 5 patients (60%)). Contrastingly, only 16 out of 56 patients (28.5%) in the control group had a positive MSLN score. Based on Fisher’s exact test, a near significant association was observed between positive MSLN score and future development of cancer recurrence (p: 0.06). No statistical significance was observed between positive MSLN score and location of metastases (SOM vs PM) likely due to limited sample size. A higher proportion of patients who had a recurrence (SOM+PC groups) had a positive MSLN score on their resected CRC specimens compared to the patients who did not recur (control group) (p: 0.06). MSLN staining results on the remaining patients is ongoing. Precision medicine informatics to identify patients at highest risk of development of future recurrence is key to personalize treatment for patients with colorectal cancer.