Despite advances in early diagnosis and surgical treatment, the prognosis for patients with primary malignant tumors of the hepatobiliary tract and pancreas has not changed markedly over the last decades. Early metastatic relapse after complete resection indicates the presence of disseminated tumor cells undetectable by current tumor staging methods. Sensitive immunohistocytochemical and nucleic acid-based assays have been developed to detect single tumor cells present in lymph nodes, bone marrow, or blood. Standardization of the current occult tumor cell detection protocols are needed before "micrometastatic" tumor staging can be used in clinical practice. We present an overview of recent studies on the frequency and prognostic value of occult disseminated tumor cells in the lymph nodes, bone marrow, and blood of patients with hepatopancreatobiliary malignancies and metastatic colorectal cancer identified by immunohistocytochemistry or nucleic acid-based assays.