Tumor stage in bowel and breast cancer is the chief determinant of prognosis and the need for adjuvant therapy. The intermediate filament protein keratin 19 (K19) is expressed by epithelia and corresponding malignancies. Recently, the detection of K19 gene expression by RT-PCR has been reported as a sensitive tool for detecting occult metastasis to the lymph nodes and bone marrow of patients with primary epithelial tumors. Doubt has arisen, however, about the tissue specificity of K19 gene expression. In this study, we report a comparison of RT-PCR for K19 with another keratin, K20, in the lymph nodes and bone marrow of 15 patients with colorectal cancer, eight control patients who underwent bowel resection for benign disease, and four other control patients. K19 and K20 gene expression was detected in 84 and 26 of 109 lymph nodes and in 6 and 0 of 15 bone marrow aspirates, respectively, from colorectal cancer patients. K19 gene expression was also detected in 34 of 40 lymph nodes and in 5 of 12 bone marrow aspirates from control patients, whereas K20 gene expression was undetectable in any control sample. In conclusion, K19 RT-PCR lacks specificity as a marker of occult lymph node and bone marrow metastasis. In contrast, K20 RT-PCR was specific and should be evaluated further in future studies.