e19029 Background: The ability of metastases to spawn subsequent generations of metastatic lesions is controversial, and its prognostic significance is unknown. We hypothesize that melanoma metastases that have spread to draining lymph nodes will have a worse prognosis than those that have not. Methods: One hundred consecutive patients who had undergone pulmonary resection for metastatic melanoma and who had concomitant hilar and/or mediastinal lymph node evaluation available were identified. Patient demographics, tumor characteristics, mediastinal lymph node status, and overall survival were analyzed. Results: 100 patients (71%) were male and the mean age at metastasectomy was 55 years (mean age at diagnosis 47 years.) The average Breslow thickness was 2.43mm (range 0.46 – 20.55). Twenty-one (21%) of the patients had evidence of metastatic disease present in regional lymph nodes during pulmonary resection. The 5-year overall survival for patients with positive mediastinal lymph nodes was 16% versus 36% with node negative disease (p=0.0005). On multivariate analysis, age at pulmonary resection (HR 1.018, 95% CI 1.002-1.035) and regional lymph nodes status (HR 3.203, 95% CI 1.774-5.781) were found to be independent prognostic indicators of 5-year overall survival. Conclusions: Regional lymph node status is an important prognostic factor in patients with pulmonary metastatic melanoma, and regional nodal assessment should be considered during metastasectomy. The metastatic cascade appears to be a strong prognostic factor in melanoma.