Background:Primary localized cutaneous amyloidosis is classified into three major forms: macular amyloidosis with rippled hyperpigmentation often on the back and upper arms, papular (lichen) amyloidosis with hyperpigmented papules often in a rippled pattern mainly on the extensor surface of extremities and back and nodular amyloidosis. Various modalities were used in the treatment of cutaneous amyloidosis including various types of lasers, but results were disappointing.Objective: To assess the efficacy of fractional CO2 laser in the treatment of macular and papular amyloidosis both clinically and histologically.Methods: A total of 25 patients, 16 with macular amyloidosis and 9 with lichen amyloidosis (seventeen patients were females (68%) and 8 patients (32%) were males) with a mean age of 36.8±8.6 years, ranging from 23 to 50 years were treated by 3-4 sessions of fractional CO2 laser with two modalities of treatment (superficial ablative mode performed on 2 squares a, b and called area A and rejuvenative mode performed on other 2 squares c, d and called area C. All lesions were examined clinically & histologically before therapy and one month after the end of therapy to assess the degree of improvement. The lesions are evaluated clinically, histologically and by image analysis for detection of the amount of amyloid present, melanin present, thickness of the epidermis and depth of rete ridges.Results:All areas of the lesions showed significant decrease of pigmentation scores after treatment, significant drop in the frequency of rippling (p < 0.001), improvement of lichenification in macular amyloidosis, flattening of papules in lichen amyloidosis and decrease of itching significantly. As regards the histological improvement, there was a significant decrease of amyloid amount after treatment.On the other hand, there was no significant change of the amount of melanin after treatment. This applied to the two treatment types. There was significant decrease of epithelial height in treatment zone A after treatment (p = 0.032), while the decrease was apparent, but not statistically significant, in zone C (p = 0.069). Also there was significant decrease of depth of rete ridges in the 2 treatment zones after treatment (p = 0.002). Treatment was highly satisfactory for 14 patients (56%). Eight patients (32%) reported moderate degree of satisfaction, while only 3 patients (12%) had mild satisfaction with treatment. There was no significant difference between the two treatment modalities regarding clinical and histological improvement. Minimal complications occurred in the form of PIH (2 patients) and pixilation (2 patients). None of the patients suffered pain, ulceration or infection.Conclusion: Fractional CO2 laser effectively improved the appearance of macular and lichen amyloidosis after 3-4 sessions with minimal complications.