To evaluate the role of epiluminescence microscopy (ELM) in the differential diagnosis of cutaneous pigmented lesions, and to improve the early diagnosis of cutaneous malignant melanoma (CMM), 15,719 pigmented lesions from 8782 consecutive patients were evaluated using ELM with a hand-held video microscope imaging system (MS 500B Micro-Scopeman, Moritex). Comparison between risk levels as inferred from ELM screening and histology was performed on 2731 surgically excised lesions. ELM sensitivity, specificity, positive and negative predictive values, as well as agreement with histological results for the different subgroups of lesions, were determined. Overall agreement was 87.3% (ranging from 85.1% to 92.2% for melanocytic and non-melanocytic lesions, respectively); sensitivity and specificity were high (values ranging from 87.3% to 96.3% among different subsets of ELM-analysed lesions) and statistically significant (P < 0.0001). ELM screening identified 165 new cases of CMM with a high proportion of lesions (115; 70%) in an early phase of tumour growth (Breslow thickness </= 1.5 mm). Thus, ELM is helpful to the clinician in deciding which pigmented lesions need surgical excision, as well as in diagnosing early CMM lesions.