SUMMARY:: Palindromic sequences, or inverted repeats (IRs), in DNA sequences involve important biological processes such as DNA–protein binding, DNA replication and DNA transposition. Development of bioinformatics tools that are capable of accurately detecting perfect IRs can enable genome-wide studies of IR patterns in both prokaryotes and eukaryotes. Different from conventional string-comparison approaches, we propose a novel algorithm that uses a cumulative score system based on a prime number representation of nucleotide bases. We then implemented this algorithm as a MATLAB-based program for perfect IR detection. In comparison with other existing tools, our program demonstrates a high accuracy in detecting nested and overlapping IRs. AVAILABILITY AND IMPLEMENTATION:: The source code is freely available on (http://bioinfolab.miamioh.edu/bioinfolab/palindrome.php) CONTACT:: liangc@miamioh.edu or karroje@miamioh.edu SUPPLEMENTARY INFORMATION:: Supplementary data are available at Bioinformatics online.