BACKGROUND: About 20% of small cell lung cancer (SCLC) patients have bone marrow (BM) metastasis at the time of diagnosis and the remaining patients are also considered with micrometastasis. In an att empt to detect BM micrometastasis, we used cytokeratin (CK)-20 as a molecular marker, which is specific for epithelial cells. METHOD: A sensitive RT-PCR assay was used to compare CK-20 expression both in SCLC cell line H209 and normal leukocyte and to evaluate BM aspirates of 28 SCLC patients. RESULT: H209 cell line showed CK-20 expression but normal leukocyte did not, suggesting CK-20 expression is lung tissue-specific. Of 28 patients (11 limited disease, 17 extensive disease), only 2 (1/11, 1/17) samples tested revealed positive signal for CK-20. Two patients with CK-20 expression had BM metastasis or multiple bone involvement during follow-up. CONCLUSION: Although circulating tumor cells were detected in BM of small portion of patients with bone metastasis, CK-20 doesn't seem to be a reliable marker for the detection of micrometastasis in SCLC. This study emphasizes that identification of more specific marker for micromatastsis is mandatory prior to clinical application.