MicroRNAs (miRs) are small non-coding RNAs which post-transcriptionally modulate gene expression. Sequence-specific interactions with target mRNAs allow miRs to influence many aspects of cellular function, treatment response and tumorigenesis1. We have previously profiled transcript abundance of mRNAs and miRs across 57 unique lines of the Ludwig Melbourne melanoma cell line panel2. Cell lines were classified as epithelial-like (E) or mesenchymal-like (M) on the basis of prototypical gene expression, principally ECAD or NCAD. Differential expression analysis was performed on microRNA abundance between the E and M groups. Target genes of statistically significantly differentially-expressed miRs were identified from the DIANA-microT database, with subsequent pathway enrichment analysis using DIANA Mir-Path_v2. MicroRNA abundance independently and accurately clustered E or M cell lines without reference to gene expression data. Target genes of differentially-expressed miRs were enriched for genes involved in PI3K-AKT/phosphatidylinositol, MAPK, ErbB and insulin signalling; axonal/synaptic function; multiple cancers; and melanogenesis. Genes targeted by multiple miRs were associated with pathway enrichment of the p53, VEGF and mTOR pathways. B and T cell receptor signalling were both represented by the most-highly targeted gene, NFAT5. Interaction analysis of genes targeted by multiple miRs revealed nodes of interest for further mechanistic exploration.