OBJECTIVE To determine whether 6 weeks could replace 3 months for short-term sequential digital dermoscopy imaging (ST-SDDI) of suspicious melanocytic lesions and determine the proportion of melanomas missed. DESIGN Consecutive lesions (n = 2602) undergoing ST-SDDI monitored from 1859 patients were included. Half of the patients underwent 6-week monitoring followed by 3-month monitoring (range, 2.5-4.5 months) if changes were not seen. The remainder underwent 3-month monitoring only. Any change during this time led to excision. Lesions unchanged were then followed up over time. SETTING A tertiary referral institution. MAIN OUTCOME MEASURES The proportion of changed melanomas (sensitivity) and odds ratios (ORs) for melanoma of changed lesions. RESULTS Eighty-one melanomas were detected using ST-SDDI (Breslow thickness: median, in situ; maximum, 0.8 mm). Of 39 melanomas detected using ST-SDDI in the 6-week monitored lesions, 27 (69%) were detected at 6 weeks and 12 (31%) at 3 months. The OR for melanoma for a lesion changing at 6 weeks was 19 (95% confidence interval [CI], 10-35), and the overall OR for melanoma for a lesion changing during the short-term monitoring period (6 weeks to 4.5 months) was 47 (95% CI, 23-94). For lesions remaining unchanged at 3 months, 99.2% (1118 of 1127 lesions) were shown to be benign as defined by an unremarkable further follow-up. Seventy-five percent (15 of 20) of the lentigo maligna melanomas, 93% (40 of 43) of other in situ melanomas, and 96% (26 of 27) of the invasive melanomas were detected using ST-SDDI. Conclusion Three months remains the standard interval for ST-SDDI, where the sensitivity for the diagnosis of melanoma for changed (non-lentigo maligna) lesions is high but not 100%.