This book constitutes the refereed proceedings of the 21st Annual Symposium on Combinatorial Pattern Matching, CPM 2010, held in New York, USA, in June 2010. The 28 revised full papers presented together with 3 invited talks were carefully reviewed and selected from 53 submissions. The papers address all areas related to combinatorial pattern matching and its applications, such as searching and matching strings and more complicated patterns such as trees, regular expressions, graphs, point sets, and arrays with special focus on coding and data compression, computational biology, data mining, information retrieval, natural language processing, pattern recognition, string algorithms, string processing in databases, symbolic computing and text searching.