There is lack of studies on the diagnostic accuracy of dermatoscopy and reflectance confocal microscopy (RCM) for dark pigmented lesions.To assess the diagnostic accuracy of dermatoscopy plus confocal microscopy for melanoma diagnosis of dark pigmented lesions in real life.Prospective analysis of difficult dark lesions with clinical-dermatoscopic suspicion of melanoma referred to RCM for further analysis. Outcome of lesions could be: excision or dermatoscopic digital follow up.We included 370 clinically dark lesions from 350 patients (median age, 45 years). Due to the clinical-dermatoscopic-RCM approach, we saved 129/213 unnecessary biopsies (specificity of 60.6%) with a sensitivity of 98.1% (154/157). Number needed to excise with the addition of RCM was 1.5 for melanoma diagnosis.Single institution based; Italian population only.This study demonstrated that RCM coupled with dermatoscopy increase the specificity for diagnosing melanoma and it helps to correctly identify benign lesions. Our findings provide the basis for subsequent prospective studies on melanocytic neoplasms belonging to patients in different countries.