Background The effects of primary tumor size on nodal involvement and of number of involved nodes on survival have not, to our knowledge, been examined in a national database of Merkel cell carcinoma (MCC). Objective We sought to analyze a retrospective cohort of patients with MCC from the largest US national database to assess the relationships between these clinical parameters and survival. Methods A total of 8044 MCC cases in the National Cancer Data Base were analyzed. Results There was a 14% risk of regional nodal involvement for 0.5-cm tumors that increased to 25% for 1.7-cm (median-sized) tumors and to more than 36% for tumors 6 cm or larger. The number of involved nodes was strongly predictive of survival (0 nodes, 76% 5-year relative survival; 1 node, 50%; 2 nodes, 47%; 3-5 nodes, 42%; and ≥6 nodes, 24%; P < .0001 for trend). Younger and/or male patients were more likely to undergo pathological nodal evaluation. Limitations The National Cancer Data Base does not capture disease-specific survival. Hence, relative survival was calculated by comparing overall survival with age- and sex-matched US population data. Conclusion Pathologic nodal evaluation should be considered even for patients with small primary MCC tumors. The number of involved nodes is strongly predictive of survival and may help improve prognostic accuracy and management.