Macular amyloidosis (MA) is one of the most common types of primary localized cutaneous amyloidosis (PLCA), distributed predominantly over the trunk and extremities. Due to the vast therapeutic options, this study aims to compare the effectiveness of Q-switched Nd: YAG laser 1064 nm and Er: YAG laser 2940 nm in treating MA. This clinical trial was performed in 2020–2021 on 33 women with MA. In each patient, the lesion was randomly divided into two areas, A and B. Area A underwent four treatment sessions with 4-week intervals of Q-switched Nd: YAG laser 1064 nm. Area B underwent four treatment sessions with an Er: YAG laser 2940 nm at 4-week intervals. Degree of basal pigmentation and degree of pigmentation after treatment, pruritus intensity, before and after the treatment, and patient and physicians’ satisfaction were measured and compared. The pruritus in patients improved significantly after the study ( P  < 0.001), but no significant differences could be observed between the two groups regarding the improvements ( P  > 0.05). We also found no significant differences between the two groups of patients regarding patient and physicians’ satisfaction rates ( P  > 0.05). The use of both Q-switched Nd: YAG laser and Er: YAG laser resulted in improvements in terms of pruritus, patient and physicians’ satisfaction, and total improvement in pigmentation of the lesions.