ComiR is a web tool for combinatorial microRNA (miRNA) target prediction. Given an messenger RNA (mRNA) in human, mouse, fly or worm genomes, ComiR computes the potential of being targeted by a set of miRNAs, each of which can have zero, one or more targets on its 3′untranslated region. In determining the regulatory potential of an mRNA from a set of miRNAs, ComiR uses user-provided miRNA expression levels in a combination of appropriate thermodynamic modeling and machine learning techniques to make more accurate predictions. For each gene, ComiR returns the probability of being a functional target of a set of miRNAs, which depends on the relative miRNA expression levels. The tool provides a user-friendly interface to input a miRNA expression table containing many sample information and filter out the most relevant miRNAs. ComiR results can be downloaded or visualized on a table, which can then be used to select the most relevant targets and to compare the results obtained with different miRNA expression input. ComiR is freely available for academic use athttp://www.benoslab.pitt.edu/comir/.