Introduction Primary squamous cell carcinoma of the colon is a rare malignancy, especially in the postpartum period. Currently, there are no recommended guidelines for this disease. BRAFV600E-mutated metastatic colorectal cancer occurs in approximately 8–12% of patients with colorectal cancer. Case presentation Herein, we report a case of a 37-year-old Chinese woman diagnosed with postpartum descending colon squamous cell carcinoma harboring the BRAFV600E mutation, which was treated with radical resection and adjuvant chemotherapy combined with targeted therapy. Eight months later, a new lesion was detected in the colon 40 cm away from the first mass. The patient was enrolled in a clinical trial but withdrew following two treatment cycles because of rapid disease progression. Subsequently, the patient died approximately 6 months after enrolling in the trial. Conclusion Squamous cell carcinoma of the colon, particularly in postpartum women, is uncommon and often associated with an advanced stage and poor prognosis. Presently, patients with colorectal cancer carrying the BRAFV600E mutation typically exhibit a low ratio, an advanced stage, and limited response to existing treatment approaches, resulting in a poor prognosis. Considerable emphasis and effort must be devoted to colonic squamous cell carcinoma, specifically cases harboring the BRAFV600E mutation.
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