OBJECTIVE. The aim of this study was to determine the order of melanoma nodal metastases. SUMMARY BACKGROUND DATA. Most solid tumors are thought to demonstrate a random nodal metastatic pattern. The incidence of skip nodal metastases precluded the use of sampling procedures of first station nodal basins to achieve adequate pathological staging. Malignant melanoma may be different from other malignancies in that the cutaneous lymphatic flow is better defined and can be mapped accurately. The concept of an orderly progression of nodal metastases is radically different than what is thought to occur in the natural history of metastases from most other solid malignancies. METHODS. The investigators performed preoperative and intraoperative mapping of the cutaneous lymphatics from the primary melanoma in an attempt to identify the "sentinel" lymph node in the regional basin. All patients had primary melanomas with tumor thicknesses > 0.76 mm and were considered candidates for elective lymph node dissection. The sentinel lymph node was harvested and submitted separately to pathology, followed by a complete node dissection. The null hypothesis tested was whether nodal metastases from malignant melanoma occurred in equal proportions among sentinel and nonsentinel nodes. RESULTS. Forty-two patients met the criteria of the protocol based on prognostic factors of their primary melanoma. Thirty-four patients had histologically negative sentinel nodes, with the rest of the nodes in the basin also being negative. Thus, there were no skip metastases documented. Eight patients had positive sentinel nodes, with seven of the eight having the sentinel node as the only site of disease. In these seven patients, the frequency of sentinel nodal metastases was 92%, whereas none of the higher nodes had documented metastatic disease. Nodal involvement was compared between the sentinel and nonsentinel nodal groups, based on the binomial distribution. Under the null hypothesis of equality in distribution of nodal metastases, the probability that all seven unpaired observations would demonstrate that involvement of the sentinel node is 0.008. CONCLUSIONS. The data presented demonstrate that nodal metastases from cutaneous melanoma are not random events. The sentinel lymph nodes in the lymphatic basins can be mapped and identified individually, and they have been shown to contain the first evidence of melanoma metastases. This information can be used to revolutionize melanoma care so that only those patients with evidence of nodal metastatic disease are subjected to the morbidity and expense of a complete node dissection. Because sentinel node histology accurately reflects the histology of the remainder of the lymphatic basin, information gained from the sentinel node biopsy can be used as a prognostic factor for melanoma. These findings demonstrate effective pathologic staging, no decrease in standards of care, and a reduction of morbidity with a less aggressive, rational surgical approach.