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: [email protected] or [email protected] SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.