Comparative genomics has become an essential approach for identifying homologous gene candidates and their functions, and for studying genome evolution. We developed GenomeBlast, a web tool for comparative analysis of multiple small genomes. It uses the blastp program for sequence similarity comparison and the maximum parsimony method based on gene content to infer genome phylogeny. Alignment coverage is used to identify global similarity between genes. This strategy takes advantage of the fast BLAST algorithm, and at the same time avoids finding only locally similar sequences but identifies gene-wide similarities (more likely to be homologue candidates). With GenomeBlast, the following results can be obtained: (1) unique genes in each genome; (2) homologous gene candidates among compared genomes; (3) 2D plots of homologous gene candidates along the all pairwise genome comparisons; (4) a table of gene presence/absence information and a genome phylogeny. Compared with outer similar tools, GenomeBlast is unique in that it integrates all the above functions, and all are easily accessible by the users through a simple web interface. In this report, we demonstrate the functions included in GenomeBlast with an example of multiple herpes viral genome analysis and how GenomeBlast is useful for small genome comparison.