BACKGROUND: The accurate staging of patients with breast cancer is essential to its management and prognosis. Sentinel node biopsy appears to offer an alternative to routine axillary lymph node dissection for staging breast cancer patients. Current method of routine histopathologic analysis of dissected lymph nodes may be inadequate because up to 30% of patients free of lymph node metastases develop a relapse in 5 to 10 years. Recently, the development of amplification of MUC1 mRNA and keratin 19 mRNA by RT-PCR for detection of micrometastases in breast cancer has been shown to be a sensitive and useful diagnostic method. This study was performed to evaluate the usefulness of MUC1 mRNA and keratin 19 mRNA markers by RT-PCR to detect micrometastases in frozen sections of sentinel lymph nodes from breast cancer patients and to identify which histopathologic prognostic factors were related to RT-PCR detected micrometastases. METHODS: The incidence of axillary micrometastases in 15 sentinel lymph node specimens from 15 patients who underwent breast cancer surgery with sentinel lymphadenectomy was from June 1999 to July 1999 was studied. Complete axillary dissection was made in all of the patients. Each sentinel lymph node specimen was examined by hematoxylin and eosin (H&E) staining, immunohistochemical cyto keratin (IHC) staining and RT-PCR on adjacent sections to determine the expression of the mRNA tumor marker of MUC1 and keratin 19. All of the dissected lymph nodes were examined by serial sectioning. RESULTS: Fourteen out of 15 sentinel lymph nodes were histologically negative in usual H&E staining. Serial sectioning, immunohistochemical (IHC) staining for cytokeratin demonstrated micrometastases in one, two histologically negative sentinel nodes, respectively, and MUC1 mRNA was detected in all of them. Of the 12 sentinel lymph nodes that were diagnosed to be devoid of micrometastases by IHCand serial sectioning, MUC1 mRNA was expressed in 6 nodes, indicating the presence of micrometastases. Micrometastases detected by RT-PCR were significantly correlated with tumor size, expression of p53 and negative PR in conventionally lymph node-negative staged patients. CONCLUSION: The MUC1 mRNA RT-PCR was more sensitive than immunohistochemistry and serial sectioning for the detection of micrometastases in axillary lymph nodes, but keratin 19 was not specific. Sentinel lymph node biopsy with RT-PCR is a more useful means of detecting micrometastases and may have a role in identifying a group of patients who will benefit from earlier adjuvant chemotherapy, but the prognostic significance must be determined after a longer follow-up.