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<p>Abstract</p> <p>Background</p> <p><it>Streptomyces coelicolor</it>, a model organism of antibiotic producing bacteria, has one of the largest genomes of the bacterial kingdom, including 7825 predicted protein coding genes. A large number of these genes, nearly 34%, are functionally orphan (hypothetical proteins with unknown function). However, in gene expression time course data, many of these functionally orphan genes show interesting expression patterns.</p> <p>Results</p> <p>In this paper, we analyzed all functionally orphan genes of <it>Streptomyces coelicolor </it>and identified a list of "high priority" orphans by combining gene expression analysis and additional phylogenetic information (i.e. the level of evolutionary conservation of each protein).</p> <p>Conclusions</p> <p>The prioritized orphan genes are promising candidates to be examined experimentally in the lab for further characterization of their function.</p>