In human solid cancer, the lymph node (LN) status is the most important prognostic indicator for the clinical outcome of patients. Recent developments in the sentinel lymph node (SLN) concept and technology have resulted in the application of this revolutionary approach to define the first draining or SLN to which the cancer may have metastasized. The underlying thesis in solid cancer biology is that metastasis generally starts in an orderly progression, spreading through the lymphatic channels to the SLN in the nearest LN basin. Thus, the logical approach is to harvest that specific SLN for thorough analysis. Because a tumorfree SLN is usually associated with a negative residual LN basin, a negative SLN is an excellent indication that micrometastasis has not occurred in the regional LNs. When the SLN is involved, it is unknown whether or not metastasis is limited only to the SLN or if the disease has spread to the remainder of the nodal basin. For this reason, if a SLN is positive, a complete lymph node dissection is recommended. Therefore, selective sentinel lymphadenectomy (SSL) should be considered as a staging procedure so that patients with negative SLNs (about 80%) may be spared an extensive LN dissection. Malignant melanoma has been proven to be the most ideal tumor model to study the role of SLN. Subsequently, SSL has been applied to breast cancer, colon cancer and other types of solid cancer. The multidisciplinary approach encompassing the surgeon, nuclear medicine physician, and pathologist is the key to such a successful procedure. Such a team can be formed readily with appropriate training. Beyond the technical aspects of harvesting the SLN, the implication of micrometastasis remains to be defined. Because the follow-up of melanoma and breast cancer patients after SSL is crucial, ongoing clinical trials are in progress to determine the biological and clinical significance of SLNs. Although the concept of SLN is viable in other types of cancer, such as gynecological and gastrointestinal, the technical aspects of the procedure need to be perfected and verified. The most exciting possibility of SSL is that it will lead to early diagnosis of micrometastasis in regional LNs. Early diagnosis makes it useful as a clinical staging procedure, and opens up new opportunities to study micrometastasis and its evolution within the SLNs. Examining the multifaceted aspects of micrometastasis, such as differentiation of different clones with respect to the primary tumor, acquisition of adhesion molecules, and host interaction with the microscopic tumor, will shed new light on the biology of early metastasis. New molecular and genetic tools may be used to dissect the mechanisms of lymphatic and hemo togenous routes of metastasis. If such mechanisms can be understood, new therapeutic advances may be developed to prevent the process of micrometastasis. Rather than targeting larger tumor burdens such as Stage IV disease, targeted adjuvant clinical trials can be developed for high risk patients following definit ive surgical resection. SSL is a standard staging procedure for patients with melanoma and is rapidly evolving into a standard procedure for breast cancer as well.