Of more than 38,000 pancreatic cyst molecular analyses performed between March 2010 and October 2019, we identified 3332 patients that underwent serial DNA analysis. We reviewed serial test results to better understand how DNA abnormalities (DNA Ab) or the lack thereof, may remain stable, regress, or progress to cumulative levels associated with high risk of malignancy. Most patients who had non-worrisome levels of DNA Ab (≤1) continued to have non-worrisome levels at 1.5 years follow-up. Given the high negative predictive value for test results based on the lack of cumulative DNA damage, these data suggest that in patients with pancreatic cysts that contain no DNA Ab, surveillance intervals may be lengthened beyond 1 year. Although molecular regression can occur in patients with multiple (2-3) DNA Ab, a significant fraction of these patients will retain their cumulative DNA damage over time, consistent with higher risk disease.