BACKGROUND Digital dermoscopy monitoring (DDM) is an effective strategy for melanoma detection. Two methods are currently employed. Short-term follow-up (STFU) for the evaluation of single, atypical lesions to detect subtle changes over a short period of time (3-6 months). Long-term follow-up (LTFU) is recommended for patients with multiple nevi. Although a study demonstrated that STFU improves the patients' compliance for DDM, little remains known about the impact and reliability of STFU in this setting. OBJECTIVES The aim of this retrospective, observational study was to evaluate the impact and reliability of a schedule combining STFU and LTFU in patients with multiple atypical nevi. METHODS We searched our database for all cases of patients with multiple atypical nevi occurring between 2006 and 2014. RESULTS A total of 3823 lesions in 541 patients were dermoscopically monitored (mean number = 7 lesions per patient; median = 6 lesions; range, 2-51). In all, 264 (6.9%) lesions in 184 (34.4%) patients were excised (mean of 0.5 lesions per patient). In total, 197 (74.6%) lesions were excised at follow-up, with melanomas representing 30.5% of lesions excised after follow-up. A total of 30 (33.3%) melanomas were excised at baseline, 23 (25.6%) after STFU and 37 (41.1%) after LTFU. There was no difference in the number of in situ melanomas detected at baseline with those detected after follow-up. The mean Breslow thickness of melanomas detected at baseline was higher than those detected after STFU (P = 0.038) and LTFU (P = 0.055). CONCLUSIONS Our study confirm that digital dermoscopy follow-up is a valid management strategy for patients with multiple atypical nevi, with short-term monitoring playing an effective role also in this setting of patients.