An enucleated globe was submitted from an outside hospital to the Ophthalmic Pathology Laboratory for evaluation. There was a minimal amount of accompanying clinical history. Histopathologic examination revealed a mucinous adenocarcinoma of the choroid. The determination of the origin of the tumor proved to be challenging based on the lack of a definitive systemic diagnosis. Initial suspicions that the tumor may represent a breast carcinoma were disproved when immunohistochemical biomarkers for breast carcinoma were negative. Similarly, typical markers of colon adenocarcinoma were not expressed. Positive immunostaining with a newer immunohistochemical marker, SATB2, and defects in DNA mismatch repair helped to confirm that the ocular metastasis was of colonic origin. Further clinical evaluation including imaging studies established that the patient had a primary colonic adenocarcinoma with widespread systemic metastases. The diagnostic utility and biologic significance of these latest immunohistochemical biomarkers for colon cancer are reviewed. Clinicians are encouraged to provide detailed clinical histories with the tissue specimens to enable the discovery of undetected “silent primaries” at the time an ocular metastasis develops and is discovered.