INTRODUCTION:Guanylyl cyclase C appears to be expressed only in colorectal cancer cells in extraintestinal tissues. Thus, guanylyl cyclase C may be useful as a marker to detect colorectal cancer micrometastases not detectable by histopathology in lymph nodes of patients.METHODS:Twelve patients with colon adenocarcinoma, Dukes Stages A through C2, and one patient with a tubulovillous adenoma were included in this study. Forty‐two lymph nodes were collected from fresh surgical specimens, and each was examined by histopathology and reverse transcription followed by polymerase chain reaction using guanylyl cyclase C‐specific primers. Histopathology identified colon cancer cells in 6 of 16 lymph nodes from five Dukes Stage C patients but not in lymph nodes from the patient with a tubulovillous adenoma, the Dukes Stage A patient, or six Dukes Stage B patients. Reverse transcription followed by polymerase chain reaction using guanylyl cyclase C‐specific primers was performed on all 42 lymph nodes.RESULTS:Guanylyl cyclase C messenger RNA was not detected by reverse transcription followed by polymerase chain reaction in lymph nodes from the patient with the tubulovillous adenoma or the patient with Dukes Stage A colon carcinoma. Seven lymph nodes from Dukes Stage C patients revealed guanylyl cyclase C messenger RNA including six lymph nodes containing histopathologically confirmed metastases. Of significance, guanylyl cyclase C messenger RNA was detected in 6 of 21 lymph nodes from Dukes Stage B patients. Indeed, clinical staging of two patients could be upgraded from B to C using reverse transcription followed by polymerase chain reaction and guanylyl cyclase C‐specific primers.CONCLUSION:Reverse transcription followed by polymerase chain reaction using guanylyl cyclase C‐specific primers might be useful to more accurately assess micrometastases in lymph nodes of colorectal cancer patients undergoing disease staging.