As advances in technology allow for the collection, storage, and analysis of vast amounts of data, the task of screening and assessing the significance of discovered patterns is becoming a major challenge in data mining applications. In this work, we address significance in the context of frequent itemset mining. Specifically, we develop a novel methodology to identify a meaningful support threshold s* for a dataset, such that the number of itemsets with support at least s* represents a substantial deviation from what would be expected in a random dataset with the same number of transactions and the same individual item frequencies. These itemsets can then be flagged as statistically significant with a small false discovery rate. We present extensive experimental results to substantiate the effectiveness of our methodology.