A storage system comprises a cache for caching data blocks and storage devices for storing blocks. A storage operating system may deduplicate sets of redundant blocks on the storage devices based on a deduplication requirement. Blocks in cache are typically deduplicated based on the deduplication on the storage devices. Sets of redundant blocks that have not met the deduplication requirement for storage devices and have not been deduplicated on the storage devices and cache are targeted for further deduplication processing. Sets of redundant blocks may be further deduplicated based on their popularity (number of accesses) in cache. If a set of redundant blocks in cache is determined to have a combined number of accesses being greater than a predetermined threshold number of accesses, the set of redundant blocks is determined to be “popular.” Popular sets of redundant blocks are selected for deduplication in cache and the storage devices.