OBJECTIVES: Melanoma is the fifth most common cancer in the UK, accounting for 4% of all new cases of skin cancer. In 2011, 13,300 cases of malignant melanoma were diagnosed in the UK, out of which 2,200 people died from the disease. This systematic review evaluates the clinical effectiveness of VivaScope (MAVIG GmbH, Munich), a non-invasive reflectance confocal microscope (RCM), used following dermoscopy for the diagnosis of melanoma. This research was conducted as part of a National Institute for Health and Care Excellence (NICE) Diagnostic Assessment Report on VivaScope. METHODS: Electronic databases (MEDLINE, EMBASE and the Cochrane Library) were searched in October 2014 and updated in February 2015 to identify studies evaluating RCM following dermoscopy with histopathology as the reference standard in detecting malignant melanoma. Researchers were contacted for additional information on studies identified. Clinical experts were contacted for details on any unpublished studies. RESULTS: Of the 7,446 studies identified in the literature search, 10 were considered relevant to this review. However, none were conducted in the UK (1 Spain, 1 China, 1 Australia, 2 Brazil/USA, 2 Australia/Italy, 3 Italy) and the studies were considered too heterogeneous (e.g. differences in study design, patient/lesion level data, with/without comparator) for their results to be combined in a meta-analysis. Overall results indicate that RCM subsequent to dermoscopy may improve diagnostic accuracy of malignant melanomas compared to dermoscopy alone. One study (Alarcon et al.