Atypical pigmented lesions (dysplastic naevi) are excised as a precautionary measure as they mimic the appearance of primary melanoma. The subsequent histopathological diagnosis of lesions is often straightforward based on architectural hallmarks and cytological criteria. However, there is a proportion of lesions which are inconclusive in their pathological presentation which may lead to unnecessary wide-local excision (WLE) and increased follow-up surveillance. It is clear that we require better tools to correctly distinguish between naevi and melanoma to serve as a companion diagnostic tool. Previously, we identified a panel of ‘melanoma-related’ microRNAs (‘MELmiR-17’) that was able to predict the stage, recurrence and survival of patients when it was measured in melanoma tissues derived from metastases (stage III and IV). In this current pilot study, we assessed this panel in a range of archival melanocytic lesions (n=37) which included 20 benign/dysplastic naevi, 11 melanoma in situ (MIS) and 6 thin melanoma. All specimens were firstly microscope-guided macro-dissected prior to total RNA extraction. Total RNA was also prepared from whole sections including non-lesional skin, as a comparison. The MELmir-17 panel was measured using a custom Taqman-assay pool and detected using the BioMark™ HD (Fluidigm). When naevi were compared to melanoma, miRNA panel members were able to accurately distinguish benign vs malignant and benign vs dysplastic for macro-dissected and whole sections. In most cases dysplastic naevi were similar to MIS which mirrors the difficulty of providing an accurate histopathological diagnosis. When macro-dissected tissue was compared with whole sections; as an example, miR-211 (pigment-cell specific) was highly correlated (R2=0.52-0.88) as were the majority. These data illustrate the potential utility of the MELmiR-17 panel as a diagnostic tool to differentiate melanoma from benign naevi. We are currently expanding the study cohorts to validate these findings – particularly in lesions with unknown malignant potential (i.e. dysplastic lesions).