Abstract Primary adenosquamous carcinoma of the colon is exceedingly rare and accounts for a clinically aggressive minority of colonic epithelial malignancies, with metastatic disease identified in 36% to 49% of cases at the time of diagnosis or resection, compared to 14% of conventional adenocarcinoma cases. Reported median overall survival time is less than half of that for conventional colonic adenocarcinoma, supporting inclusion of squamous differentiation as an adverse prognostic factor. Due to its rarity, optimal treatment protocols have yet to be standardized. We present the case of a 61-year-old female who underwent emergent right hemicolectomy due to bowel obstruction secondary to an ileocecal mass discovered on imaging. Gross examination revealed a 7.3-cm, primarily submucosal cecal mass involving the appendix with associated ileocolic adhesion. Histologic examination showed carcinoma with distinct areas of glandular and squamous differentiation, exhibiting the anticipated differential expression patterns of CK5/6, p63, CK20, CDX2, and mucicarmine. Immunohistochemistry for p16 was negative in both components. The adenocarcinoma component was continuous with a small focus of dysplastic colonic surface epithelium, supportive of cecal origin. Eight of 19 lymph nodes were positive for squamous and adenocarcinomatous metastasis, and a concurrent liver biopsy was also positive for metastasis. There was no evidence of mismatch repair protein deficiency by immunohistochemistry, which was performed on tissue containing both glandular and squamous components. We share this case to highlight a rare and uniquely aggressive subtype of a routinely encountered malignancy, reinforcing the importance of identifying and reporting squamous differentiation within cases of colonic adenocarcinoma.