Background: Because recent western studies have shown an association between genetic variation of SCN5A and sick sinus syndrome (SSS), we investigated genetic variation of SCN5A in Korean patients with SSS. Methods: We enrolled 30 patients with SSS, diagnosed as sinus pause longer than 3.0 sec in Holter monitoring, and 30 controls. All exons including the putative splicing sites of the SCN5A gene were amplified by PCR and sequenced directly or after subcloning. Results: A total of 9 genetic variations in 30 patients were identified: 7 variations (G87A-A29A, IVS9-3C>A, A1673G-H558R, G3823A-D1275N, T5457C-D1819D, T5963G-L1988R, C5129T-S1710L) had been reported previously and 2 variants (A3075T-E1025D, T4847A-F1616Y) were novel; the potential structural effects F161Y and S170L were analyzed in a three-dimensional model of the SCN5A domain. Conclusion: We found 2 novel genetic variations (E1025D, F1616Y) in the SCN5A gene in Korean patients with SSS. Further study of their functional relevance is warranted.