Determining the site of origin of metastatic adenocarcinoma lesions has obvious therapeutic and prognostic implications. Immunostaining for cytokeratin subtypes 7 and 20 is increasingly used to evaluate metastatic colorectal cancer lesions. We present the case of a patient with a history of colorectal cancer who subsequently developed an isolated metastatic lesion in the lung. As illustrated by our case, staining for cytokeratin subtypes can be helpful in determining the site of origin of metastatic lesions.