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What lesions to select for a most efficient dermatoscopic monitoring of patients with multiple nevi remains an unresolved issue.To compare the grade of atypia of melanomas and nevi of the same patient at baseline.Prospective observational study using 236 dermatoscopic baseline images (59 quartets from 59 patients, each including one melanoma detected during follow-up and three nevi). Dermatologists (n = 26) were asked to assess the ‘grade of dermatoscopic atypia’ on a numerical scale and to identify the melanomas.On average, each dermatologist identified 24 of 59 melanomas (40%, range: 11–37). The number of correct picks was greater for dermatologists with moderate (mean: 28) or high (mean: 28) experience compared to beginners (mean 17; P < 0.001). In three of the 59 sets, none of the 26 dermatologists identified the melanoma. The mean grade of dermatoscopic atypia was 2.5 for nevi (95% CI: 2.4–2.6) and 3.0 for melanomas (95% CI: 2.9–3.1, P < 0.001).Rating dermatologists were informed that each quartet of images included one melanoma creating substantial deviation from a real-life situation.A significant proportion of melanomas detected during follow-up cannot be differentiated from nevi at baseline. This necessitates the additional inclusion of less atypical lesions for monitoring.